Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning
Open accessAbstract
The production of reactive oxygen species by the mitochondrial complex II (succinate:ubiquinone oxidoreductase) recently has gained broad scientific interest. Depending on the (patho)physiological situation, ROS produced or triggered by complex II can have either beneficial or deleterious effects. This ambivalence can be explained mechanistically by the diverse role of complex II on mitochondrial ROS production: it can be a source as well as a suppressor or enhancer of ROS generation by other respiratory chain complexes. Since complex II directly links the respiratory chain to the tricarboxylic acid (TCA) cycle, the TCA-cycle intermediates - especially oxaloacetate that acts as a high affinity endogenous inhibitor - have major impact on complex II-related ROS release. The review relates the diverse effects of complex II activity on the mitochondrial ROS production that have been observed during cardioprotective ischemic or pharmacological preconditioning and the oxidative burst that occurs during ischemia/reperfusion. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 175 cited sources checked · 0 supported · 0 flagged
- Findingcitation
A 5% drop in the mitochondrial membrane potential reduces hydrogen peroxide release from isolated mitochondria by 95%.
“that a drop in ΔΨ by only 5% reduces the hydrogen peroxide release of isolated mitochondria by 95%.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] 18. T.V. Votyakova, I.J. Reynolds, ΔΨ-dependent and -independent production of re- active oxygen species by rat brain mitochondria, J. Neurochem. 79 (2001) 266-277. source
Not checked in the free run.
- Findingcitation
Experimental evidence for oxaloacetate-dependent inhibition of complex II under anoxic conditions is lacking.
“However, experimental evidence for an oxaloacetate-dependent inhibition of complex II under anoxic conditions is lacking [109].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [109] 109. E. Maklashina, A.B. Kotlyar, J.S. Karliner, G. Cecchini, Effect of oxygen on activa- tion state of complex I and lack of oxaloacetate inhibition of complex II in Langendorff perfused rat heart, FEBS Lett. 556 (2004) 64-68. source
Not checked in the free run.
- Findingcitation
In isolated rat heart mitochondria, succinate-driven superoxide production at complex I by RET can be abolished completely by 10 nM atpenin A5, a concentration that only partially inhibited succinate-dependent respiration.
“We could show in investigations with isolated rat heart mitochondria, that the succinate-driven superoxide production at complex I by RET can be abolished completely by atpenin A5 concentrations of 10 nM, a concentration that only partially inhibited succinate-dependent respiration [16].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- Findingcitation
A physiological correlate of experimentally induced antimycin A inhibition has not been identified.
“However, it has to be pointed out that a physiological correlate of the experimentally induced antimycin A inhibition has not been identified yet [25].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] 25. L. Bleier, S. Dröse, Superoxide generation by complex III: from mechanistic rationales to functional consequences, Biochim. Biophys, Acta (2013), http://dx.doi.org/10. 1016/j.bbabio.2012.12.002. source
Not checked in the free run.
- Premisecitation
Complex II activity can strongly influence ROS production by complexes I and III.
“Furthermore, it is well known that complex II activity can have major impact on the ROS production by complexes I and III [15,16].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- Premisecitation
Under conditions of reverse electron transfer, inhibiting complex II lowers complex I-related ROS generation.
“Under these conditions inhibition of complex II leads to a reduction of complex I related ROS generation [15,16,19,20,24].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- cites [19] 19. Y. Liu, G. Fiskum, D. Schubert, Generation of reactive oxygen species by the mi- tochondrial electron transport chain, J. Neurochem. 80 (2002) 780-787. source
Not checked in the free run.
- cites [20] 20. A.J. Lambert, M.D. Brand, Superoxide production by NADH:ubiquinone oxidore- ductase (complex I) depends on the pH gradient across the mitochondrial inner membrane, Biochem. J. 382 (2004) 511-517. source
Not checked in the free run.
- cites [24] 24. J.R. Treberg, C.L. Quinlan, M.D. Brand, Evidence for two sites of superoxide produc- tion by mitochondrial NADH-ubiquinone oxidoreductase (complex I), J. Biol. Chem. 286 (2011) 27103-27110. source
Not checked in the free run.
- Premisecitation
Inhibiting complex II can raise superoxide generation at the Qo site of complex III when succinate is the main substrate and electron transfer between heme bL and heme bH is slowed, such as when the Qi site is blocked by antimycin A.
“On the other hand, inhibition of complex II can increase the generation of superoxide at the ubiquinol oxidation site (Q o site) of complex III under specific conditions [25], i.e. when succinate is the predominant substrate and when the electron transfer between heme b L (low potential heme) and heme b H (high potential heme) is slowed down additionally, e.g. when the ubiquinone reduction site of”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [25] 25. L. Bleier, S. Dröse, Superoxide generation by complex III: from mechanistic rationales to functional consequences, Biochim. Biophys, Acta (2013), http://dx.doi.org/10. 1016/j.bbabio.2012.12.002. source
Not checked in the free run.
- cites [15,16,[26][27][28][29][30][31]
Not checked in the free run.
- Premisecitation
Loss of complex II function can cause succinate accumulation and increased ROS generation in mammalian cells.
“It has been observed that loss of function of complex II can lead to the accumulation of succinate and increased ROS generation in mammalian cells (overview in [14,36]).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [14] 14. T.M. Iverson, E. Maklashina, G. Cecchini, Structural basis for malfunction in com- plex II, J. Biol. Chem. 287 (2012) 35430-35438. source
Not checked in the free run.
- cites [36] 36. S.J. Ralph, R. Moreno-Sanchez, J. Neuzil, S. Rodriguez-Enriquez, Inhibitors of suc- cinate: quinone reductase/complex II regulate production of mitochondrial re- active oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death, Pharm. Res. 28 (2011) 2695-2730. source
Not checked in the free run.
- Premisecitation
Ishii and coworkers found that an SdhC mutation in transgenic mouse fibroblasts and conditional transgenic mice induces mitochondrial respiratory chain dysfunction and increased ROS production.
“Ishii and coworkers observed that a mutation in the SdhC subunit in transgenic mouse fibroblasts and conditional transgenic mice induces mitochondrial respiratory chain dysfunction and increased ROS production [95].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [95] 95. T. Ishii, M. Miyazawa, A. Onodera, K. Yasuda, N. Kawabe, M. Kirinashizawa, S. Yoshimura, N. Maruyama, P.S. Hartman, N. Ishii, Mitochondrial reactive oxygen species generation by the SDHC V69E mutation causes low birth weight and neonatal growth retardation, Mitochondrion 11 (2011) 155-165. source
Not checked in the free run.
- Premisecitation
In Quinlan et al.'s experiments, contributions of complexes I and III to the detected ROS were excluded by rotenone and myxothiazol.
“A significant contribution of complexes I and III to the detected ROS generation could be excluded by the addition of rotenone (that inhibits ROS production by RET at complex I) and myxothiazol (that inhibits ROS production at the Q o site of complex III and at the same time served as the downstream block).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
- Interpretationcitation
Complex II inhibitors have ambivalent effects on mitochondrial ROS production that depend on substrate supply, membrane potential, and the overall activities of respiratory chain and TCA cycle enzymes.
“Hence, it is not surprising that complex II inhibitors show ambivalent effects on mitochondrial ROS production [15,16] depending on substrate supply, membrane potential and overall activities of respiratory chain and TCA cycle enzymes.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- Interpretationcitation
The ROS-promoting effect of complex II inhibitors can be explained by a partially oxidized Q-pool that maximizes complex III ROS production during antimycin inhibition.
“This ROS-promoting effect of complex II inhibitors can be related to a partially oxidized Q-pool that maximizes ROS production by complex III upon antimycin inhibition [25,32,33].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [25] 25. L. Bleier, S. Dröse, Superoxide generation by complex III: from mechanistic rationales to functional consequences, Biochim. Biophys, Acta (2013), http://dx.doi.org/10. 1016/j.bbabio.2012.12.002. source
Not checked in the free run.
- cites [32] 32. S. Dröse, U. Brandt, The mechanism of mitochondrial superoxide production by the cytochrome bc 1 complex, J. Biol. Chem. 283 (2008) 21649-21654. source
Not checked in the free run.
- cites [33] 33. C.L. Quinlan, A.A. Gerencser, J.R. Treberg, M.D. Brand, The mechanism of super- oxide production by the antimycin-inhibited mitochondrial Q-cycle, J. Biol. Chem. 286 (2011) 31361-31372. source
Not checked in the free run.
- Premisecitation
Under hypoxic conditions, succinate concentration rises to several millimolar.
“However, several studies have shown that the succinate concentration increases under hypoxic conditions up to values of several millimolar [22,72,[74][75][76][77][78].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22,72,[74][75][76][77][78]
Not checked in the free run.
- Premisecitation
The Km values of complex II and the dicarboxylate carrier for succinate are approximately 1 mM.
“The K m values of complex II and the dicarboxylate carrier that catalyzes transport of succinate into the mitochondria are around 1 mM [70,71].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [70] 70. F. Palmieri, G. Prezioso, E. Quagliarello, M. Klingenberg, Kinetic study of dicarboxylate carrier in rat liver mitochondria, Eur. J. Biochem. 22 (1971) 66-74. source
Not checked in the free run.
- cites [71] 71. B.A. Ackrell, E.B. Kearney, T.P. Singer, Mammalian succinate dehydrogenase, Methods Enzymol. 53 (1978) 466-483. source
Not checked in the free run.
- Premisecitation
Complex II inhibitors have protective effects in various model systems when given during preconditioning phases or during reperfusion.
“In this context, complex II inhibitors have been shown to exert protective effects in different model systems during preconditioning phases or when they were present during reperfusion [41][42][43][44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41][42][43][44]
Not checked in the free run.
- Premisecitation
Quinlan et al. showed that complex II also produced ROS in the reverse reaction when electrons were supplied from the reduced ubiquinone pool.
“Furthermore, Quinlan et al. could show that complex II also produced ROS in the reverse reaction, i.e. when the electrons are provided from the reduced ubiquinone pool [37].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
- Premisecitation
Oxaloacetate formation explains why succinate alone supports only weak state 3 respiration in isolated mitochondria.
“Oxaloacetate formation is also the reason why succinate alone is only supporting weak state 3 respiration of isolated mitochondria [65].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [65] 65. M. Gutman, E.B. Kearney, T.P. Singer, Control of succinate dehydrogenase in mi- tochondria, Biochemistry 10 (1971) 4763-4770. source
Not checked in the free run.
- Interpretationcitation
Modulation of Qo-site superoxide by complex II requires succinate as the predominant substrate and conditions of oxidant-induced reduction at complex III.
“One prerequisite for this is that succinate is the predominate substrate, another that conditions of 'oxidant-induced reductions' are applied to complex III.”
Quote in the paperSubstantial claim - Premisecitation
Complex I inhibitors such as rotenone, FMN-compromising inhibitors, and NADH-binding-site inhibitors suppress ROS generation under reverse electron transfer conditions in intact mitochondria and coupled submitochondrial particles.
“investigations with different experimental systems (intact mitochondria and coupled SMP) revealed that different complex I inhibitors like the Q-site inhibitor rotenone or inhibitors that compromise the primary electron acceptor FMN or the NADH binding site suppressed ROS generation under conditions of reverse electron transfer [18][19][20]24,91,92].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18][19][20]24,91,92]
Not checked in the free run.
- Premisecitation
The strongest argument for the ROS-by-reverse-electron-transfer hypothesis is that ROS production is highly sensitive to even small changes in membrane potential.
“Whereas a contribution of other componentsespecially the DLD (dihydrolipoamide dehydrogenase) component of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase [22,107] cannot be excluded, the strongest argument for the 'ROS by RET' hypothesis is that ROS production is highly sensitive to even small changes in membrane potential [18].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] 18. T.V. Votyakova, I.J. Reynolds, ΔΨ-dependent and -independent production of re- active oxygen species by rat brain mitochondria, J. Neurochem. 79 (2001) 266-277. source
Not checked in the free run.
- Interpretationreasoning
Increased reduction of FAD in the dicarboxylate binding site, whether from intrinsic redox-center properties or from mutation or inhibition of downstream redox centers, raises the risk of ROS production under aerobic conditions.
“This suggests that an increased reduction of FAD in the dicarboxylate binding siteeither by differential intrinsic properties and arrangements of the redox centers, or mutations/inhibition of downstream located redox centerscauses an increased risk for ROS production under aerobic conditions.”
Quote in the paperSubstantial claim - Premisecitation
Isolated mitochondria produce large amounts of ROS when incubated with succinate as the sole or equally supplied substrate.
“It is well known that isolated mitochondria produce large quantities of ROS when they are incubated with succinate as the sole or equally supplied substrate source [17][18][19][20][21][22][23].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17][18][19][20][21][22][23]
Not checked in the free run.
- Interpretationcitation
Oxaloacetate inhibition of complex II has developed as a mechanism to minimize RET-mediated superoxide production.
“Furthermore, it can be concluded that the oxaloacetate inhibition of complex II has developed as a mechanism to minimize RET-mediated superoxide production [23].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] 23. F.L. Muller, Y.H. Liu, M.A. Abdul-Ghani, M.S. Lustgarten, A. Bhattacharya, Y.C. Jang, H. Van Remmen, High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I-and complex II-linked substrates, Biochem. J. 409 (2008) 491-499. source
Not checked in the free run.
- Premisecitation
Votyakova and Reynolds determined that a 5% drop in membrane potential reduces hydrogen peroxide release from isolated mitochondria by 95%.
“In a detailed analysis, Votyakova and Reynolds determined that a drop in ΔΨ by only 5% reduces the hydrogen peroxide release of isolated mitochondria by 95%.”
Quote in the paperSubstantial claim - Interpretationreasoning
The differential effects of complex II on mitochondrial ROS production are influenced by succinate concentration and the activity of other respiratory chain complexes.
“In summary, the differential effects of complex II on mitochondrial ROS production seem to be influenced by the succinate concentration and the activity of the other respiratory chain complexes.”
Quote in the paperSubstantial claim - Interpretationreasoning
Suppression of ROS generation by higher substrate concentrations strengthens the model that complex II generates ROS when FAD is reduced and the dicarboxylate binding site is unoccupied.
“Especially the suppression of ROS generation by higher substrate concentrations (which leaves the redox state of the redox centers largely unaffected) strengthens the latter model indicating that complex II generates ROS when the FAD is reduced and the dicarboxylate binding site is not occupied.”
Quote in the paperSubstantial claim - Premisecitation
A high rate of ROS production is observed when NADH-generating substrates and succinate are supplied together to isolated mitochondria.
“A high rate of ROS production is also observed when NADH-generating substrates and succinate are concomitantly supplied to isolated mitochondria [21,23,34,35].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [21] 21. F. Zoccarato, L. Cavallini, S. Bortolami, A. Alexandre, Succinate modulation of H 2 O 2 release at NADH:ubiquinone oxidoreductase (complex I) in brain mito- chondria, Biochem. J. 406 (2007) 125-129. source
Not checked in the free run.
- cites [23] 23. F.L. Muller, Y.H. Liu, M.A. Abdul-Ghani, M.S. Lustgarten, A. Bhattacharya, Y.C. Jang, H. Van Remmen, High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I-and complex II-linked substrates, Biochem. J. 409 (2008) 491-499. source
Not checked in the free run.
- cites [34] 34. F. Zoccarato, L. Cavallini, A. Alexandre, Succinate is the controller of O 2 -•/H 2 O 2 release at mitochondrial complex I: negative modulation by malate, positive by cyanide, J. Bioenerg. Biomembr. 41 (2009) 387-393. source
Not checked in the free run.
- cites [35] 35. F. Zoccarato, C. Miotto, L. Cavallini, A. Alexandre, The control of mitochon- drial succinate-dependent H 2 O 2 production, J. Bioenerg. Biomembr. 43 (2011) 359-366. source
Not checked in the free run.
- Premisecitation
Under specific conditions with pyruvate and glutamate, supplementation with only 15-150 micromolar succinate is enough to significantly increase ROS release from isolated mitochondria.
“Under some specific conditions (i.e. in presence of pyruvate and glutamate), a supplementation of only 15-150 μM succinate is enough to increase ROS release from isolated mitochondria significantly [34].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] 34. F. Zoccarato, L. Cavallini, A. Alexandre, Succinate is the controller of O 2 -•/H 2 O 2 release at mitochondrial complex I: negative modulation by malate, positive by cyanide, J. Bioenerg. Biomembr. 41 (2009) 387-393. source
Not checked in the free run.
- Interpretationreasoning
Under succinate-supported reverse electron transfer conditions, complex II activity is necessary to reduce ubiquinol that fuels complexes III and IV to generate the proton-motive force required for RET.
“Under these conditions complex II activity is necessary for the reduction of ubiquinol that fuels the respiratory chain complexes III and IV to generate the proton-motive force that is required for RET (Fig. 3A).”
Quote in the paperSubstantial claim - Interpretationreasoning
A large membrane potential is a prerequisite for driving electrons against the redox potential gradient from complex II into complex I.
“This indicates that a large membrane potential is prerequisite to drive the electrons against the gradient of redox potentials from complex II into complex I.”
Quote in the paperSubstantial claim - Interpretationreasoning
Inhibition of complex II reduces the membrane potential by diminishing electron supply to downstream respiratory chain complexes.
“Inhibition of complex II reduces the membrane potential by diminishing the electron supply for the downstream respiratory chain complexes.”
Quote in the paperSubstantial claim - Interpretationnone given
Inhibitors of the dicarboxylate binding site attenuate ROS production at complex II.
“Importantly, inhibitors of the dicarboxylate binding site will attenuate ROS production at complex II.”
Quote in the paperSubstantial claim - Premisereasoning
Reduction of complex II activity increases ROS generation by antimycin A-inhibited complex III.
“Anyway, the reduction of complex II activity leads to an increase of the ROS generation by the antimycin A-inhibited complex III [15,16,[26][27][28][29][30][31]33].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15,16,[26][27][28][29][30][31]33]
Not checked in the free run.
- Premisecitation
Complex II inhibitors that bind the dicarboxylate site or the Qp site attenuate ROS production when succinate is the prevalent substrate.
“The ROS production is also attenuated by complex II inhibitors that bind either to the dicarboxylate site or the Qp site if succinate is the prevalent substrate [15,16,19,20,24].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- cites [19] 19. Y. Liu, G. Fiskum, D. Schubert, Generation of reactive oxygen species by the mi- tochondrial electron transport chain, J. Neurochem. 80 (2002) 780-787. source
Not checked in the free run.
- cites [20] 20. A.J. Lambert, M.D. Brand, Superoxide production by NADH:ubiquinone oxidore- ductase (complex I) depends on the pH gradient across the mitochondrial inner membrane, Biochem. J. 382 (2004) 511-517. source
Not checked in the free run.
- cites [24] 24. J.R. Treberg, C.L. Quinlan, M.D. Brand, Evidence for two sites of superoxide produc- tion by mitochondrial NADH-ubiquinone oxidoreductase (complex I), J. Biol. Chem. 286 (2011) 27103-27110. source
Not checked in the free run.
- Interpretationown data
Complex II predominantly produces ROS from reduced FAD at low succinate concentrations and when the downstream electron transfer chain is blocked.
“Complex II predominantly produces ROS from reduced FAD at low succinate concentrations and when the downstream electron transfer chain is blocked (Fig. 3C).”
Quote in the paperSubstantial claim - Premisecitation
Under very specific conditions, complex II can modulate superoxide production at the Qo site of complex III.
“Under very specific conditions, complex II can also modulate the superoxide production at the Q o site of complex III [15,16,33] (Fig. 3B).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- cites [33] 33. C.L. Quinlan, A.A. Gerencser, J.R. Treberg, M.D. Brand, The mechanism of super- oxide production by the antimycin-inhibited mitochondrial Q-cycle, J. Biol. Chem. 286 (2011) 31361-31372. source
Not checked in the free run.
- Premisecitation
Complex II is recognized as a modulator of superoxide production by other mitochondrial enzymes, especially complexes I and III.
“Apart from the direct generation of ROS (Section 3.1), complex II has been recognized as a modulator of the superoxide production by other mitochondrial enzymes, especially the respiratory chain complexes I and III [15,16,25] that are generally regarded as main ROS sources in the mitochondria [3][4][5][6].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- cites [25] 25. L. Bleier, S. Dröse, Superoxide generation by complex III: from mechanistic rationales to functional consequences, Biochim. Biophys, Acta (2013), http://dx.doi.org/10. 1016/j.bbabio.2012.12.002. source
Not checked in the free run.
- cites [3][4][5][6]
Not checked in the free run.
- Premisecitation
Diazoxide and other complex II inhibitors such as malonate and atpenin A5 exert protective effects in isolated cardiomyocytes and Langendorff-perfused rat hearts when added before the long ischemic/reperfusion period.
“Diazoxide and other complex II inhibitors like malonate and atpenin A 5 can also exert protective effects in different model systems (isolated cardiomyocytes, Langendorff-perfused rat hearts) when they are added prior to the long damage-inducing ischemic/ reperfusion period [42][43][44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42][43][44]
Not checked in the free run.
- Premisecitation
Under these specific conditions, an intermediate succinate concentration/complex II activity results in an intermediate reduction of the Q-pool that favors superoxide production by complex III.
“Under these specific conditions, an intermediate succinate concentration/complex II activity results in an intermediate reduction of the Q-pool that favors superoxide production by complex III [32].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] 32. S. Dröse, U. Brandt, The mechanism of mitochondrial superoxide production by the cytochrome bc 1 complex, J. Biol. Chem. 283 (2008) 21649-21654. source
Not checked in the free run.
- Interpretationcitation
The lower H2O2 scavenger activity with succinate may be explained by the membrane-bound transhydrogenase depending on a constant NADH supply.
“This might be explained by the fact that one of the main NADP + -reducing enzymes in the mitochondria, the membrane-bound transhydrogenase [118], depends on a constant NADH supply.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [118] 118. J. Rydström, Mitochondrial NADPH, transhydrogenase and disease, Biochim. Biophys. Acta 1757 (2006) 721-726. source
Not checked in the free run.
- Interpretationnone given
Qp site inhibitors induce ROS production at low succinate concentrations.
“In contrast, Qp site inhibitors will induce ROS production at low succinate concentrations.”
Quote in the paperSubstantial claim - Premisecitation
Malonate and diazoxide attenuate ROS generation after and during ischemia and upon reperfusion in isolated rat heart mitochondria.
“It has been shown that malonate and diazoxide, a well known opener of ATP-gated K + -channels (K ATP channels), can attenuate the ROS generation that occurs after and during an ischemic period and upon reperfusion in isolated rat heart mitochondria [41][42][43].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41][42][43]
Not checked in the free run.
- Interpretationreasoning
Considering succinate accumulation under hypoxic/ischemic conditions, RET-dependent ROS production by complex I seems a likely candidate for the ROS burst.
“Considering the accumulation of succinate under hypoxic/ischemic conditions (Section 2.2), the RET-dependent ROS production by complex I seems to be a likely candidate (Fig. 3A).”
Quote in the paperSubstantial claim - Premisecitation
Reactive oxygen species are a main factor contributing to damage during ischemia/reperfusion.
“Reactive oxygen species are a main factor contributing to the damage during I/R [8].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] 8. A.P. Halestrap, S.J. Clarke, I. Khaliulin, The role of mitochondria in protection of the heart by preconditioning, Biochim. Biophys. Acta 1767 (2007) 1007-1031. source
Not checked in the free run.
- Interpretationreasoning
Oxaloacetate could act as a physiological suppressor or regulator of ROS production by complex II.
“In this regard, oxaloacetate could act as a physiological suppressor or regulator of the ROS production by complex II.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Complex III inhibitors such as stigmatellin, myxothiazol, or antimycin A inhibit succinate-dependent ROS by RET because complex III inhibition collapses the membrane potential.
“Also complex III inhibitors like stigmatellin, myxothiazol or antimycin A will inhibit succinate-dependent ROS by RET, because the membrane potential collapses upon complex III inhibition.”
Quote in the paperSubstantial claim - Interpretationreasoning
Both classes of complex II inhibitors increase superoxide production at the Qo site of complex III under oxidant-induced reduction conditions, when the Qi site is blocked and succinate is the predominant substrate.
“Finally, both classes of complex II inhibitors will increase superoxide production at the Q o site of complex III under conditions of 'oxidant-induced reduction', i.e. when the Q i site of complex III is blocked and when succinate is the predominate substrate (Fig. 3B).”
Quote in the paperSubstantial claim - Premisecitation
H2O2 scavenger activities of isolated mitochondria are lower with succinate as the sole substrate than with NADH-generating substrates like malate/glutamate or malate/pyruvate.
“In this context, it is important to note that the H 2 O 2 scavenger activities of isolated mitochondria are lower with succinate as the sole substrate than with NADH-generating substrates like malate/glutamate or malate/pyruvate [111,112].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [111] 111. F. Zoccarato, L. Cavallini, A. Alexandre, Respiration-dependent removal of exog- enous H 2 O 2 in brain mitochondria -inhibition by Ca 2+ , J. Biol. Chem. 279 (2004) 4166-4174. source
Not checked in the free run.
- cites [112] 112. D.A. Drechsel, M. Patel, Respiration-dependent H 2 O 2 removal in brain mitochon- dria via the thioredoxin/peroxiredoxin system, J. Biol. Chem. 285 (2010) 27850-27858. source
Not checked in the free run.
- Premisecitation
Mitochondria play a central role in reperfusion injury, since mPTP induction upon calcium overload and oxidative stress leads to apoptotic and necrotic cell death.
“Mitochondria seem to play a central role in reperfusion injury, since the induction of the mitochondrial permeability transition pore (mPTP) upon calcium-overload and oxidative stress leads finally to apoptotic and necrotic cell death [8,122].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] 8. A.P. Halestrap, S.J. Clarke, I. Khaliulin, The role of mitochondria in protection of the heart by preconditioning, Biochim. Biophys. Acta 1767 (2007) 1007-1031. source
Not checked in the free run.
- cites [122] 122. A.P. Halestrap, P. Pasdois, The role of the mitochondrial permeability transition pore in heart disease, Biochim. Biophys. Acta 1787 (2009) 1402-1415. source
Not checked in the free run.
- Premisecitation
Diazoxide inhibits mitochondrial complex II.
“In addition to the interaction with K ATP channels, diazoxide has been shown to inhibit mitochondrial complex II [15,[126][127][128][129].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15,[126][127][128][129]
Not checked in the free run.
- Interpretationnone given
Activities of complexes III and IV are necessary for generating the high membrane potential prerequisite for ROS by RET.
“The activities of complexes III and IV are necessary for the generation of a high membrane potential that is prerequisite for ROS by RET.”
Quote in the paperSubstantial claim - Interpretationnone given
Antimycin A inhibition increases superoxide generation at the Qo site.
“However, inhibition by antimycin A will increase the superoxide generation at the Q o site.”
Quote in the paperSubstantial claim - Premisecitation
In isolated rat heart mitochondria, complex II inhibitors increase superoxide production at the Qo site of complex III only under specific conditions: succinate is the predominant substrate and oxidant-induced reduction occurs.
“In isolated rat heart mitochondria, complex II inhibitors can increase the superoxide production at the Q o site of complex III only under the specific conditions indicated in Section 3.2 and Fig. 3B [15,16,33], i.e. when succinate is the predominant substrate and under conditions of 'oxidant-induced reduction'.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- cites [33] 33. C.L. Quinlan, A.A. Gerencser, J.R. Treberg, M.D. Brand, The mechanism of super- oxide production by the antimycin-inhibited mitochondrial Q-cycle, J. Biol. Chem. 286 (2011) 31361-31372. source
Not checked in the free run.
- Interpretationreasoning
This might explain why a ROS-increasing effect of diazoxide has not been detected with NADH-generating substrates or without complex III inhibition.
“This might explain why a ROS-increasing effect of diazoxide has not been detected in the presence of NADH-generating substrates or when complex III was not inhibited [129,138,139].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [129] 129. S. Dröse, U. Brandt, P.J. Hanley, K + -independent actions of diazoxide question the role of inner membrane K ATP channels in mitochondrial cytoprotective sig- naling, J. Biol. Chem. 281 (2006) 23733-23739. source
Not checked in the free run.
- cites [138] 138. R. Ferranti, M.M. da Silva, A.J. Kowaltowski, Mitochondrial ATP-sensitive K + channel opening decreases reactive oxygen species generation, FEBS Lett. 536 (2003) 51-55. source
Not checked in the free run.
- cites [139] 139. H.T.F. Facundo, R.S. Carreira, J.G. de Paula, C.C.X. Santos, R. Ferranti, F.R.M. Laurindo, A.J. Kowaltowski, Ischemic preconditioning requires increases in reac- tive oxygen release independent of mitochondrial K + channel activity, Free Radic. Biol. Med. 40 (2006) 469-479. source
Not checked in the free run.
- Interpretationreasoning
The ROS-reducing properties of complex II inhibitors during reperfusion might be explained by reduction of the membrane potential required for superoxide generation at complex I via RET.
“Mechanistically, the ROS-reducing properties of complex II inhibitors during reperfusion might be explained by the reduction of the membrane potential (Fig. 3A) that is required for the generation of superoxide at complex I via reverse electron transfer.”
Quote in the paperSubstantial claim - Interpretationreasoning
Recent publications challenging the existence of reverse electron transfer from complex II into complex I have not considered the requirement of complexes III and IV for high membrane potential.
“This has not been considered in recent publications that have challenged the existence of a reverse electron transfer from complex II into complex I [36,110].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [36] 36. S.J. Ralph, R. Moreno-Sanchez, J. Neuzil, S. Rodriguez-Enriquez, Inhibitors of suc- cinate: quinone reductase/complex II regulate production of mitochondrial re- active oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death, Pharm. Res. 28 (2011) 2695-2730. source
Not checked in the free run.
- cites [110] 110. R. Moreno-Sanchez, L. Hernandez-Esquivel, N.A. Rivero-Segura, A. Marin-Hernandez, J. Neuzil, S.J. Ralph, S. Rodriguez-Enriquez, Reactive oxygen species are generated by the respiratory complex II: evidence for lack of contribution of the reverse electron flow in complex I, FEBS J. (2012), http://dx.doi.org/10.1111/febs12086, (published online as).
Not checked in the free run.
- Premisecitation
This mechanism is supported by several studies with isolated mitochondria.
“Such a mechanism is supported by several studies with isolated mitochondria [15,16,19,20,24].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
- cites [19] 19. Y. Liu, G. Fiskum, D. Schubert, Generation of reactive oxygen species by the mi- tochondrial electron transport chain, J. Neurochem. 80 (2002) 780-787. source
Not checked in the free run.
- cites [20] 20. A.J. Lambert, M.D. Brand, Superoxide production by NADH:ubiquinone oxidore- ductase (complex I) depends on the pH gradient across the mitochondrial inner membrane, Biochem. J. 382 (2004) 511-517. source
Not checked in the free run.
- cites [24] 24. J.R. Treberg, C.L. Quinlan, M.D. Brand, Evidence for two sites of superoxide produc- tion by mitochondrial NADH-ubiquinone oxidoreductase (complex I), J. Biol. Chem. 286 (2011) 27103-27110. source
Not checked in the free run.
- Interpretationnone given
There is increasing evidence that complex II can be a major regulator of mitochondrial ROS production under physiological and pathophysiological circumstances.
“There is increasing evidence that complex II (succinate:ubiquinone oxidoreductase) can be a major regulator of mitochondrial ROS production under physiological and pathophysiological circumstances.”
Quote in the paperNot a substantial claim - Interpretationcitation
This can be explained by the pronounced sensitivity of RET toward small changes in ΔΨ.
“This can be explained by the pronounced sensitivity of RET toward small changes in ΔΨ [18].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] 18. T.V. Votyakova, I.J. Reynolds, ΔΨ-dependent and -independent production of re- active oxygen species by rat brain mitochondria, J. Neurochem. 79 (2001) 266-277. source
Not checked in the free run.
- Interpretationnone given
Complex II can adapt different roles as a producer or modulator of mitochondrial ROS depending on substrate supply and the activities of other respiratory chain complexes and TCA cycle enzymes.
“In doing so, complex II can adapt different roles as a producer or modulator of mitochondrial ROS depending on substrate supply and the activities of the other respiratory chain complexes and TCA cycle enzymes.”
Quote in the paperSubstantial claim - Premisecitation
Higher concentrations of atpenin A5 that inhibit complex II activity were needed in Langendorff-perfused hearts to induce cardioprotection.
“However, higher concentrations of atpenin A5that were shown to inhibit complex II activityhad to be used in Langendorf-perfused hearts to induce a cardioprotective effect [44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] 44. A.P. Wojtovich, P.S. Brookes, The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial K-ATP channels, Basic Res. Cardiol. 104 (2009) 121-129. source
Not checked in the free run.
- Premisecitation
Atpenin A5 had the same cardioprotective effects in cardiomyocytes and Langendorff-perfused rat hearts as ischemic preconditioning, diazoxide, and malonate.
“Importantly, the results of Wojtovich and Brookes indicate that the highly potent and specific complex II inhibitor atpenin A5 had the same cardioprotective effects in cardiomyocytes and Langendorff-perfused rat hearts as ischemic preconditioning, diazoxide, and malonate [44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] 44. A.P. Wojtovich, P.S. Brookes, The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial K-ATP channels, Basic Res. Cardiol. 104 (2009) 121-129. source
Not checked in the free run.
- May combine two claims. 45
- Classified as probably not a substantial claim. 33
May combine two claims.
Findingown dataThe modulation of mitochondrial ROS production by atpenin A5 was independent of K+ ions, indicating that a putative mitoKATP channel was not involved.
“Importantly, the modulation of mitochondrial ROS production was independent of K + -ions, indicating that a putative mitoK ATP channel was not involved.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationSimilar atpenin A5 concentrations stimulated superoxide production at the Qo site of antimycin A-inhibited complex III, which may represent the source of signaling ROS during ischemic and pharmacological preconditioning.
“In addition, similar atpenin A5 concentrations stimulated the superoxide production at the Q o site of antimycin A inhibited complex III, which may represent the source of 'signaling ROS' during ischemic and pharmacological preconditioning [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSome complex II subunit mutations linked to cancer or neurodegeneration can increase ROS generation.
“However, some mutations in complex II subunits that have been linked to specific forms of cancer or neurodegeneration can lead to an increased ROS generation (reviewed in [12][13][14]).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12][13][14]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe respiratory chain supplies most ATP in eukaryotic cells and is also a major source of reactive oxygen species.
“The respiratory chain provides the main portion of ATP in eukaryotic cells, but is also a major source of reactive oxygen species (ROS) [2][3][4][5][6].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2][3][4][5][6]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationComplex II oxidizes succinate to fumarate and reduces ubiquinone, thereby directly connecting the TCA cycle to the respiratory chain.
“Mitochondrial complex II (succinate:ubiquinone oxidoreductase; succinate dehydrogenase, SDH) oxidizes succinate to fumarate and reduces ubiquinone, thereby creating a direct link between the tricarboxylic acid (TCA) cycle (also known as citric acid or Krebs cycle) and the respiratory chain [1] (Fig. 1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] 1. G. Cecchini, Function and structure of complex II of the respiratory chain, Annu. Rev. Biochem. 72 (2003) 77-109. source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationComplexes I and III are generally viewed as the main ROS sources in the respiratory chain, while intact complex II is thought to contribute negligibly.
“Within the respiratory chain, complexes I (NADH:ubiquinone oxidoreductase) and III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc 1 complex) are generally regarded as the main ROS sources, while the contribution of intact complex II seems to be negligible [3][4][5][6].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3][4][5][6]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMutations in complex II subunits C and D near the Qp site are associated with hereditary paragangliomas and pheochromocytomas, and SdhA mutations can cause Leigh syndrome.
“This seems to be especially the case for mutations in complex II subunits C and D located in the vicinity of the Qp site that have been associated with specific forms of cancer such as hereditary paragangliomas and pheochromocytomas (overview in [13,14,36]) and in SdhA that can cause Leigh syndrome, a progressive neurodegenerative disease [14,94].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [13] 13. C. Bardella, P.J. Pollard, I. Tomlinson, SDH mutations in cancer, Biochim. Biophys. Acta 1807 (2011) 1432-1443. source
Not checked in the free run.
- cites [14] 14. T.M. Iverson, E. Maklashina, G. Cecchini, Structural basis for malfunction in com- plex II, J. Biol. Chem. 287 (2012) 35430-35438. source
Not checked in the free run.
- cites [36] 36. S.J. Ralph, R. Moreno-Sanchez, J. Neuzil, S. Rodriguez-Enriquez, Inhibitors of suc- cinate: quinone reductase/complex II regulate production of mitochondrial re- active oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death, Pharm. Res. 28 (2011) 2695-2730. source
Not checked in the free run.
- cites [94] 94. B.A. Ackrell, Cytopathies involving mitochondrial complex II, Mol. Aspects Med. 23 (2002) 369-384. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationThe increased succinate pool under hypoxia may come from glutamate via alpha-ketoglutarate by transamination or from partial reversal of the TCA cycle from malate through fumarate, which would require complex II to act as a fumarate reductase.
“This increased succinate pool under hypoxia might be supplied either from glutamate through α-ketoglutarate by transamination [76,77] or by a partial reversal of the TCA cycle from malate through fumarate, which requires that complex II would become a fumarate reductase under hypoxia [36,79].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [76] 76. R.J. Wiesner, P. Rosen, M.K. Grieshaber, Pathways of succinate formation and their contribution to improvement of cardiac-function in the hypoxic rat-heart, Biochem. Med. Metab. Biol. 40 (1988) 19-34. source
Not checked in the free run.
- cites [77] 77. R.J. Wiesner, A. Deussen, M. Borst, J. Schrader, M.K. Grieshaber, Glutamate degra- dation in the ischemic dog heart -contribution to anaerobic energy-production, J. Mol. Cell. Cardiol. 21 (1989) 49-59. source
Not checked in the free run.
- cites [36] 36. S.J. Ralph, R. Moreno-Sanchez, J. Neuzil, S. Rodriguez-Enriquez, Inhibitors of suc- cinate: quinone reductase/complex II regulate production of mitochondrial re- active oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death, Pharm. Res. 28 (2011) 2695-2730. source
Not checked in the free run.
- cites [79] 79. C. Hohl, R. Oestreich, P. Rosen, R. Wiesner, M. Grieshaber, Evidence for succinate production by reduction of fumarate during hypoxia in isolated adult-rat heart-cells, Arch. Biochem. Biophys. 259 (1987) 527-535. source
Not checked in the free run.
May combine two claims.
PremisecitationE. coli SQR exclusively produces superoxide, whereas QFR produces mainly superoxide at lower succinate concentrations and relatively more hydrogen peroxide at higher succinate concentrations.
“E. coli SQR exclusively produces superoxide.In contrast, E. coli QFR produces mainly superoxide at lower succinate concentrations and comparably more hydrogen peroxide at higher substrate concentrations [101].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [101] 101. K.R. Messner, J.A. Imlay, Mechanism of superoxide and hydrogen peroxide for- mation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase, J. Biol. Chem. 277 (2002) 42563-42571. source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationQuinlan et al. proposed that complex II generates ROS only when the flavin is reduced and the carboxylate binding site is unoccupied.
“They proposed a mechanism for ROS production by complex II that relies upon the occupancy of the carboxylate binding site and the reduction state of the enzyme, i.e.ROS are only generated when the flavin is reduced and the carboxylate binding site is not occupied.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
May combine two claims.
Premiseown dataE. coli SQR and QFR show maximal ROS at intermediate succinate concentrations between 0.1 and 1 mM and lower rates at lower and higher substrate concentrations, resembling mammalian and nematode complex II.
“Furthermore, both enzymes showed maximal rates of ROS at intermediate succinate concentrations between 0.1 and 1 mM and decreased rates at lower and higher substrate concentration, which resembles the dependence found later for mammalian [37] and nematode [100] complex II.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
- cites [100] 100. M.P. Paranagama, K. Sakamoto, H. Amino, M. Awano, H. Miyoshi, K. Kita, Contri- bution of the FAD and quinone binding sites to the production of reactive oxy- gen species from Ascaris suum mitochondrial complex II, Mitochondrion 10 (2010) 158-165. source
Not checked in the free run.
May combine two claims.
PremisecitationComplex II activity is regulated by succinate concentration and by TCA cycle intermediates, especially oxaloacetate, which competitively inhibits complex II.
“The activity of complex II is directly influenced by the concentration of other TCA cycle metabolites, since malate, fumarate, citrate and especially oxaloacetate [65][66][67] have been shown to inhibit competitively with succinate.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [65][66][67]
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe complex II ROS production observed by Quinlan et al. was completely sensitive to malonate and only partially repressed by atpenin A5, leading them to conclude that ROS was produced at the flavin site of complex II.
“Furthermore, this ROS production was completely sensitive to the competitive carboxylate site inhibitor malonate and was only partially repressed by the Q-site inhibitor atpenin A5.Therefore, the authors concluded that the ROS must have been produced at the flavin site of complex II [37].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMessner and Imlay concluded that QFR releases superoxide from fully reduced flavin if the [2Fe-2S] cluster is available to sequester the semiquinone electron; otherwise the electron is rapidly transferred to nascent superoxide and hydrogen peroxide is released.
“Messner and Imlay concluded that QFR releases superoxide from the fully reduced flavin if the [2Fe-2S] cluster is available to sequester the semiquinone electron; otherwise this electron is rapidly transferred to the nascent superoxide and hydrogen peroxide is released [101].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [101] 101. K.R. Messner, J.A. Imlay, Mechanism of superoxide and hydrogen peroxide for- mation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase, J. Biol. Chem. 277 (2002) 42563-42571. source
Not checked in the free run.
May combine two claims.
PremisecitationMitochondrial ROS have an ambivalent role in ischemia/reperfusion and preconditioning: they contribute to cellular damage during prolonged ischemia/reperfusion but also participate in cardioprotective signaling during ischemic and pharmacological preconditioning.
“An ambivalence of mitochondrial ROS production has been also detected in the context of ischemia/reperfusion and ischemic or pharmacological preconditioning: while reactive oxygen species are among the main determinants of cellular damage during longer periods of ischemia and reperfusion, there is also ample evidence that mitochondrial ROS production is involved in cardioprotective signaling”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8,[38][39][40]
Not checked in the free run.
May combine two claims.
InterpretationcitationThe protective effects of complex II inhibitors can be explained by their differential effects on complex I and complex III ROS production: they reduce complex I reverse-electron-transfer ROS during reperfusion and promote Qo-site complex III ROS by shifting the Q-pool to an intermediate redox state.
“The protective effects of complex II inhibitors could then be explained by their differential effects on complex I and complex III related ROS production: they reduce ROS that are generated at complex I by reverse electron transfer (RET) during reperfusion while they promote production of ROS at the Q o site of complex III by shifting the redox state of the Q-pool to an intermediate state [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] 15. S. Dröse, P.J. Hanley, U. Brandt, Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III, Biochim. Biophys. Acta 1790 (2009) 558-565. source
Not checked in the free run.
- Rests on an assumption: The mechanisms of complex II-related ROS production observed in isolated mitochondria, submitochondrial particles, bacteria, and nematodes are representative of mammalian cardiac mitochondria relevant to ischemia/reperfusion and preconditioning.
May combine two claims.
PremisecitationIn coupled mitochondria and submitochondrial particles, high ROS production with saturating succinate is largely attributable to complex I via reverse electron transfer from complex II, because it is sensitive to complex I inhibitors, requires high membrane potential, and does not occur in uncoupled submitochondrial particles.
“In coupled mitochondria and SMP, high ROS production is observed under these conditions, but this can be largely attributed to complex I due to reverse electron transfer from complex II, since (i) it is sensitive to complex I inhibitors like rotenone [18][19][20]24,91,92], (ii) requires a high membrane potential, i.e. is sensitive to uncouplers and ionophores [15,[18][19][20]91] or ADP (that”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [18][19][20]24,91,92]
Not checked in the free run.
- cites [15,[18][19][20]91]
Not checked in the free run.
- cites [32] 32. S. Dröse, U. Brandt, The mechanism of mitochondrial superoxide production by the cytochrome bc 1 complex, J. Biol. Chem. 283 (2008) 21649-21654. source
Not checked in the free run.
- cites [93] 93. Q. Chen, E.J. Vazquez, S. Moghaddas, C.L. Hoppel, E.J. Lesnefsky, Production of re- active oxygen species by mitochondria: central role of complex III, J. Biol. Chem. 278 (2003) 36027-36031. source
Not checked in the free run.
May combine two claims.
Interpretationown dataIn adult Ascaris suum submitochondrial particles, succinate-dependent ROS generation was not affected by a complex I inhibitor and was completely or partially suppressed by malonate or atpenin A5, indicating that complex II was the exclusive ROS source under those conditions.
“The succinate-dependent ROS generation of SMP from adult worms, that do not contain complex III and IV activities in their respiratory chain, was not influenced by a complex I inhibitor and was completely and partially suppressed by malonate or atpenin A5, respectively.This indicates that complex II is the exclusive ROS source under these conditions.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [100] 100. M.P. Paranagama, K. Sakamoto, H. Amino, M. Awano, H. Miyoshi, K. Kita, Contri- bution of the FAD and quinone binding sites to the production of reactive oxy- gen species from Ascaris suum mitochondrial complex II, Mitochondrion 10 (2010) 158-165. source
Not checked in the free run.
May combine two claims.
PremisecitationQuinlan et al. observed that complex II in isolated rat skeletal mitochondria produced ROS at a significant rate with succinate concentrations below 5 mM, peaking around 400 micromolar, when the downstream respiratory chain was inhibited.
“This was also confirmed by Quinlan et al. [37], however these authors also observed that complex II in isolated rat skeletal mitochondria produced ROS at a significant rate with succinate concentrations below 5 mM (with a peak at around 400 μM) and when the downstream respiratory chain was inhibited.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
May combine two claims.
InterpretationcitationComplex II-related ROS rates approach or exceed the maximum rates of complexes I and III, suggesting that complex II may be an important contributor to physiological and pathological ROS production.
“Finally, it was shown that the complex II related rates approach or exceed the maximum rates of complexes I and III indicating that complex II may be an important contributor to physiological and pathological ROS production [37].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
May combine two claims.
PremisecitationE. coli SQR and QFR both produce ROS with a linear dependence on dissolved oxygen, although SQR produces ROS at a much lower rate.
“Both enzymes produced ROS with a linear dependence on the dissolved oxygen concentration, although SQR produced ROS at a much lower rate.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [101] 101. K.R. Messner, J.A. Imlay, Mechanism of superoxide and hydrogen peroxide for- mation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase, J. Biol. Chem. 277 (2002) 42563-42571. source
Not checked in the free run.
May combine two claims.
PremisecitationComplex II can oxidize malate to the enol form of oxaloacetate, which binds the dicarboxylate site with high affinity.
“Besides a direct competition between succinate and malate, it has been observed that complex II can oxidize malate to the enol form oxaloacetate [67,68], which binds to the dicarboxylate binding site with high affinity [66].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [67] 67. B.A.C. Ackrell, E.B. Kearney, M. Mayr, Studies on succinate-dehydrogenase. 24. Role of oxalacetate in regulation of mammalian succinate-dehydrogenase, J. Biol. Chem. 249 (1974) 2021-2027. source
Not checked in the free run.
- cites [68] 68. Y.O. Belikova, A.B. Kotlyar, A.D. Vinogradov, Oxidation of malate by the mitochon- drial succinate-ubiquinone reductase, Biochim. Biophys. Acta 936 (1988) 1-9. source
Not checked in the free run.
- cites [66] 66. E.B. Kearney, B.A.C. Ackrell, M. Mayr, Tightly bound oxalacetate and activation of succinated dehydrogenase, Biochem. Biophys. Res. Commun. 49 (1972) 1115-1121. source
Not checked in the free run.
May combine two claims.
InterpretationcitationUnder aerobic conditions, succinate concentrations in tissues and mitochondria are submillimolar, indicating that complex II does not operate at maximal velocity under standard conditions.
“The succinate concentration in different tissues and mitochondria is in the submillimolar range under aerobic conditions [22,72,73], indicating that complex II is not working at maximal velocity under 'standard conditions'.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [22] 22. A.A. Starkov, The role of mitochondria in reactive oxygen species metabolism and signaling, Ann. N. Y. Acad. Sci. 1147 (2008) 37-52. source
Not checked in the free run.
- cites [72] 72. S. Hoyer, C. Krier, Ischemia and the aging brain -studies on glucose and energy-metabolism in rat cerebral-cortex, Neurobiol. Aging 7 (1986) 23-29. source
Not checked in the free run.
- cites [73] 73. K. Brockmann, A. Bjornstad, P. Dechent, C.G. Korenke, J. Smeitink, J.M.F. Trijbels, S. Athanassopoulos, R. Villagran, O.H. Skjeldal, E. Wilichowski, J. Frahm, F. Hanefeld, Succinate in dystrophic white matter: a proton magnetic resonance spectroscopy finding characteristic for complex II deficiency, Ann. Neurol. 52 (2002) 38-46. source
Not checked in the free run.
May combine two claims.
InterpretationcitationIncreased oxidation of the Q-pool explains the increased ROS generation by antimycin A-inhibited complex III, because superoxide generation at the Qo site is maximal at intermediate reduction states of the ubiquinone pool when the Qi site is blocked.
“This can be explained by an increased oxidation of the Q-pool, since it was shown that the superoxide generation at the Q o site is maximal at intermediate reduction states of the ubiquinone pool if the Q i site is blocked by antimycin A [25,32,33].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [25] 25. L. Bleier, S. Dröse, Superoxide generation by complex III: from mechanistic rationales to functional consequences, Biochim. Biophys, Acta (2013), http://dx.doi.org/10. 1016/j.bbabio.2012.12.002. source
Not checked in the free run.
- cites [32] 32. S. Dröse, U. Brandt, The mechanism of mitochondrial superoxide production by the cytochrome bc 1 complex, J. Biol. Chem. 283 (2008) 21649-21654. source
Not checked in the free run.
- cites [33] 33. C.L. Quinlan, A.A. Gerencser, J.R. Treberg, M.D. Brand, The mechanism of super- oxide production by the antimycin-inhibited mitochondrial Q-cycle, J. Biol. Chem. 286 (2011) 31361-31372. source
Not checked in the free run.
May combine two claims.
PremisecitationIn SQR, high-potential centers are close to the Q site, while in QFR, FAD and the [2Fe-2S] clusters have the highest redox potentials and accumulate electrons near the dicarboxylate binding site.
“In SQR the high potential centers ([3Fe-4S] and heme b, which attract electrons and pull them away from the dicarboxylate site) are close to the Q site, while in QFR, FAD and the [2Fe-2S] clusters have the highest redox potentials and hence accumulate electrons close to the dicarboxylate binding site.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] 12. V. Yankovskaya, R. Horsefield, S. Tornroth, C. Luna-Chavez, C. Leger, B. Byrne, G. Cecchini, S. Iwata, Architecture of succinate dehydrogenase and reactive oxygen species generation, Science 299 (2003) 700-704. source
Not checked in the free run.
Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).
PremisecitationThe differential contribution of TCA cycle enzymes and the conditional removal of oxaloacetate are key factors controlling succinate-dependent ROS generation.
“it was suggested by Muller et al. that the differential contribution of TCA cycle enzymes and the conditional removal of the endogenous complex II inhibitor oxaloacetate are key factors that control succinate-dependent ROS generation [23].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] 23. F.L. Muller, Y.H. Liu, M.A. Abdul-Ghani, M.S. Lustgarten, A. Bhattacharya, Y.C. Jang, H. Van Remmen, High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I-and complex II-linked substrates, Biochem. J. 409 (2008) 491-499. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationUnder simultaneous NADH-generating substrate and succinate supply, electrons can flow downstream through complex I, which should attenuate RET.
“Zoccarato and colleagues have shown that under these conditions electrons can flow downstream through complex I, which should attenuate RET [21].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] 21. F. Zoccarato, L. Cavallini, S. Bortolami, A. Alexandre, Succinate modulation of H 2 O 2 release at NADH:ubiquinone oxidoreductase (complex I) in brain mito- chondria, Biochem. J. 406 (2007) 125-129. source
Not checked in the free run.
Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).
PremisecitationMalate reduces succinate-dependent ROS formation via accumulation of oxaloacetate that occurs unless acetyl-CoA is available.
“They have proposed that the reduction of the succinate-dependent ROS formation by malate is due to an accumulation of oxaloacetate that occurs unless acetyl-CoA is available.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] 23. F.L. Muller, Y.H. Liu, M.A. Abdul-Ghani, M.S. Lustgarten, A. Bhattacharya, Y.C. Jang, H. Van Remmen, High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I-and complex II-linked substrates, Biochem. J. 409 (2008) 491-499. source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationDifferent NADH-generating substrates have opposing effects on ROS generation.
“other studies demonstrated that different NADH-generating substrates have an opposing effect on ROS generation [23,35,108]”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [23] 23. F.L. Muller, Y.H. Liu, M.A. Abdul-Ghani, M.S. Lustgarten, A. Bhattacharya, Y.C. Jang, H. Van Remmen, High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I-and complex II-linked substrates, Biochem. J. 409 (2008) 491-499. source
Not checked in the free run.
- cites [35] 35. F. Zoccarato, C. Miotto, L. Cavallini, A. Alexandre, The control of mitochon- drial succinate-dependent H 2 O 2 production, J. Bioenerg. Biomembr. 43 (2011) 359-366. source
Not checked in the free run.
- cites [108] 108. S. Bortolami, E. Comelato, F. Zoccarato, A. Alexandre, L. Cavallini, Long chain fatty acyl-CoA modulation of H 2 O 2 release at mitochondrial complex I, J. Bioenerg. Biomembr. 40 (2008) 9-18. source
Not checked in the free run.
May combine two claims.
PremisecitationFully reduced FAD can transfer one electron to molecular oxygen to form superoxide, probably the major reaction in complex II but only confirmed for E. coli SQR, or transfer both electrons to O2 to form hydrogen peroxide, as shown for E. coli QFR.
“In principle, fully reduced FAD can either transfer one electron onto molecular oxygen which leads to the formation of superoxide (probably the major reaction in complex II, but only confirmed for E. coli SQR [101]) or it may also transfer both electrons onto O 2 which leads to the formation of H 2 O 2 (as shown for E. coli QFR [101]) (Fig. 2B).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [101] 101. K.R. Messner, J.A. Imlay, Mechanism of superoxide and hydrogen peroxide for- mation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase, J. Biol. Chem. 277 (2002) 42563-42571. source
Not checked in the free run.
May combine two claims.
PremisecitationMutants of E. coli SQR lacking heme b showed unchanged ROS generation, indicating that heme b does not serve as a sink for excess electrons.
“Mutants of E. coli SQR that do not contain heme b showed an unchanged ROS generation, indicating that this prosthetic group is not serving as a 'sink' for excess electrons [102,103].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [102] 102. Q.M. Tran, R.A. Rothery, E. Maklashina, G. Cecchini, J.H. Weiner, Escherichia coli suc- cinate dehydrogenase variant lacking the heme b, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 18007-18012. source
Not checked in the free run.
- cites [103] 103. Q.M. Tran, C. Fong, R.A. Rothery, E. Maklashina, G. Cecchini, J.H. Weiner, Out of plane distortions of the heme b of Escherichia coli succinate dehydrogenase, PLoS One 7 (2012). source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationYankovskaya et al. proposed that the key difference in ROS production between E. coli SQR and QFR lies in the differential arrangement of redox potentials among the redox centers.
“Yankovskaya et al. [12] proposed that the key difference in the ROS production by E. coli SQR and QFR lies in the differential arrangement of redox potentials among the redox centers.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] 12. V. Yankovskaya, R. Horsefield, S. Tornroth, C. Luna-Chavez, C. Leger, B. Byrne, G. Cecchini, S. Iwata, Architecture of succinate dehydrogenase and reactive oxygen species generation, Science 299 (2003) 700-704. source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe prevalent view is that under these conditions ROS are produced by complex I due to reverse electron transfer from complex II, although alternative explanations have been proposed.
“While alternative explanations for the source or mechanism of ROS production under these conditions have been proposed [34,36], the prevalent view is that under these conditions ROS are produced by complex I due to RET from complex II [18][19][20]23].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [34] 34. F. Zoccarato, L. Cavallini, A. Alexandre, Succinate is the controller of O 2 -•/H 2 O 2 release at mitochondrial complex I: negative modulation by malate, positive by cyanide, J. Bioenerg. Biomembr. 41 (2009) 387-393. source
Not checked in the free run.
- cites [36] 36. S.J. Ralph, R. Moreno-Sanchez, J. Neuzil, S. Rodriguez-Enriquez, Inhibitors of suc- cinate: quinone reductase/complex II regulate production of mitochondrial re- active oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death, Pharm. Res. 28 (2011) 2695-2730. source
Not checked in the free run.
- cites [18][19][20]23]
Not checked in the free run.
May combine two claims.
InterpretationreasoningThese redox arrangements favor the respective physiological activities and also imply a differential disposition for superoxide production under aerobic conditions.
“While these arrangements favor the respective physiological activity (i.e., ubiquinone reduction for SQR and fumarate reduction/menaquinol oxidation for QFR) they also presuppose a differential disposition for superoxide production under aerobic conditions.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] 12. V. Yankovskaya, R. Horsefield, S. Tornroth, C. Luna-Chavez, C. Leger, B. Byrne, G. Cecchini, S. Iwata, Architecture of succinate dehydrogenase and reactive oxygen species generation, Science 299 (2003) 700-704. source
Not checked in the free run.
May combine two claims.
InterpretationcitationThe most likely ROS source in wild-type complex II is the fully reduced FAD, although a Q-site contribution might occur in mutants.
“While a contribution of the Q site might occur in the respective mutants, the most likely source of ROS in wild-type complex II is the fully reduced FAD [37,101].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
- cites [101] 101. K.R. Messner, J.A. Imlay, Mechanism of superoxide and hydrogen peroxide for- mation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase, J. Biol. Chem. 277 (2002) 42563-42571. source
Not checked in the free run.
May combine two claims.
PremisecitationAtpenin A5-induced ROS generation by complex II is somewhat lower than ROS generation induced by a downstream block at the complex III Qo site, explained by altered succinate dehydrogenase activity upon atpenin A5 binding.
“However, atpenin A5 induced ROS generation by complex II was somewhat lower than ROS generation induced by a further downstream block (at the complex III Q o site by myxothialzol), which has been explained by an alteration of the succinate dehydrogenase activity upon atpenin A5 binding [37].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] 37. C.L. Quinlan, A.L. Orr, I.V. Perevoshchikova, J.R. Treberg, B.A. Ackrell, M.D. Brand, Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions, J. Biol. Chem. 287 (2012) 27255-27264. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMitochondria can scavenge large quantities of internally and externally produced ROS, especially hydrogen peroxide.
“Recent investigations indicate that mitochondria are not only an important source of ROS, but can also scavenge large quantities of internally and externally produced reactive oxygen species, especially hydrogen peroxide [22,[111][112][113][114][115][116].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22,[111][112][113][114][115][116]
Not checked in the free run.
May combine two claims.
PremisecitationInhibition of complex II and attenuation of succinate-supported ROS generation have been shown by Dzeja et al.
“Accordingly, inhibition of complex II and attenuation of the succinate supported ROS generation have been shown by Dzeja et al. [130].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [130] 130. P.P. Dzeja, P. Bast, C. Ozcan, A. Valverde, E.L. Holmuhamedov, D.G.L. Van Wylen, A. Terzic, Targeting nucleotide-requiring enzymes: implications for diazoxide-induced cardioprotection, Am. J. Physiol. 284 (2003) H1048-H1056.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningAlternatively, substrate flow through the TCA cycle differs depending on substrates, which might affect the activity of NADP+-dependent isocitrate dehydrogenase and malic enzyme.
“Alternatively, the substrate flow through the TCA cycle differs depending on the substrates, which might affect the activity of the other two mitochondrial NADPH-regenerating enzymes the NADP + -dependent isocitrate dehydrogenase [119,120] and the malic enzyme [118,121].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [119] 119. L.A. Sazanov, J.B. Jackson, Proton-translocating transhydrogenase and NAD- linked and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic-acid cycle activity in mitochondria, FEBS Lett. 344 (1994) 109-116. source
Not checked in the free run.
- cites [120] 120. S.H. Jo, M.K. Son, H.J. Koh, S.M. Lee, I.H. Song, Y.O. Kim, Y.S. Lee, K.S. Jeong, W.B. Kim, J.W. Park, B.J. Song, T.L. Huh, Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP + -dependent isocitrate dehydrogenase, J. Biol. Chem. 276 (2001) 26732. source
Not checked in the free run.
- cites [118] 118. J. Rydström, Mitochondrial NADPH, transhydrogenase and disease, Biochim. Biophys. Acta 1757 (2006) 721-726. source
Not checked in the free run.
- cites [121] 121. W.H. Ying, NAD + /NADH and NADP + /NADPH in cellular functions and cell death: regulation and biological consequences, Antioxid. Redox Signal. 10 (2008) 179-206. source
Not checked in the free run.
May combine two claims.
PremisecitationUncouplers and complex I inhibitors attenuate ROS-induced damage in ischemia/reperfusion hearts.
“They identified uncouplers and complex I inhibitors as compounds that attenuate the ROS-induced damage in I/R-hearts.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [123] 123. Q. Chen, A.K.S. Camara, D.F. Stowe, C.L. Hoppel, E.J. Lesnefsky, Modulation of electron transport protects cardiac mitochondria and decreases myocardial in- jury during ischemia and reperfusion, Am. J. Physiol. 292 (2007) C137-C147. source
Not checked in the free run.
May combine two claims.
InterpretationreasoningOverall ROS release from isolated mitochondria may appear almost unchanged under antimycin A, but ROS production shifts from complex I to complex III.
“Hence, the overall ROS release from isolated mitochondria might appear almost unchanged, yet the ROS production is shifted from complex I to complex III.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIschemic preconditioning can be mimicked by diazoxide and other substances, a phenomenon termed pharmacological preconditioning.
“Ischemic preconditioning can be mimicked by the K ATP channel opener diazoxide and various other substances, a phenomenon termed pharmacological preconditioning [39].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] 39. P.J. Hanley, J. Daut, K ATP channels and preconditioning: a re-examination of the role of mitochondrial K ATP channels and an overview of alternative mechanisms, J. Mol. Cell. Cardiol. 39 (2005) 17-50. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe mitochondrial antioxidative defense system includes the thioredoxin/peroxiredoxin system and the glutathione/glutathione peroxidase system.
“The highly effective mitochondrial antioxidative defense system encompasses the thioredoxin/peroxiredoxin system as well as the glutathione/glutathione peroxidase system (overview in [22,117]).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [22] 22. A.A. Starkov, The role of mitochondria in reactive oxygen species metabolism and signaling, Ann. N. Y. Acad. Sci. 1147 (2008) 37-52. source
Not checked in the free run.
- cites [117] 117. C.C. Winterbourn, M.B. Hampton, Thiol chemistry and specificity in redox sig- naling, Free Radic. Biol. Med. 45 (2008) 549-561. source
Not checked in the free run.
May combine two claims.
PremisecitationDiazoxide transiently induces increased ROS production, consistent with mitochondria-derived ROS being involved in cardioprotective signaling during ischemic and pharmacological preconditioning.
“Diazoxide transiently induces increased ROS production [43,[131][132][133], which is in agreement with the view that mitochondria-derived reactive oxygen species are involved in cardioprotective signaling during ischemic and pharmacological preconditioning (overview in [8,39,40]).”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [43,[131][132][133]
Not checked in the free run.
- cites [8] 8. A.P. Halestrap, S.J. Clarke, I. Khaliulin, The role of mitochondria in protection of the heart by preconditioning, Biochim. Biophys. Acta 1767 (2007) 1007-1031. source
Not checked in the free run.
- cites [39] 39. P.J. Hanley, J. Daut, K ATP channels and preconditioning: a re-examination of the role of mitochondrial K ATP channels and an overview of alternative mechanisms, J. Mol. Cell. Cardiol. 39 (2005) 17-50. source
Not checked in the free run.
- cites [40] 40. L.S. Burwell, S.M. Nadtochiy, P.S. Brookes, Cardioprotection by metabolic shut-down and gradual wake-up, J. Mol. Cell. Cardiol. 46 (2009) 804-810. source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationMitochondria are both targets and sources of injury during cardiac ischemia and reperfusion.
“It has been recognized that the mitochondria are both targets and sources of injury during cardiac ischemia and reperfusion [123].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [123] 123. Q. Chen, A.K.S. Camara, D.F. Stowe, C.L. Hoppel, E.J. Lesnefsky, Modulation of electron transport protects cardiac mitochondria and decreases myocardial in- jury during ischemia and reperfusion, Am. J. Physiol. 292 (2007) C137-C147. source
Not checked in the free run.
May combine two claims.
InterpretationreasoningROS production under these conditions is attenuated by both classes of complex II inhibitors, uncouplers, ionophores, and complex I inhibitors.
“ROS production under these conditions is therefore not only attenuated by both classes of complex II inhibitors, but also by uncouplers, ionophores and complex I inhibitors.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationIschemic preconditioning, in which brief cycles of ischemia and reperfusion precede prolonged ischemia, reduces damage from ischemia/reperfusion.
“However, the damage occurring during ischemia/reperfusion (I/R) can be reduced by ischemic preconditioning where the prolonged ischemic period is preceded by one or more brief (2-5 min) cycles of ischemia and reperfusion [8,39,124].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [8] 8. A.P. Halestrap, S.J. Clarke, I. Khaliulin, The role of mitochondria in protection of the heart by preconditioning, Biochim. Biophys. Acta 1767 (2007) 1007-1031. source
Not checked in the free run.
- cites [39] 39. P.J. Hanley, J. Daut, K ATP channels and preconditioning: a re-examination of the role of mitochondrial K ATP channels and an overview of alternative mechanisms, J. Mol. Cell. Cardiol. 39 (2005) 17-50. source
Not checked in the free run.
- cites [124] 124. D.M. Yellon, J.M. Downey, Preconditioning the myocardium: from cellular phys- iology to clinical cardiology, Phys. Rev. 83 (2003) 1113-1151. source
Not checked in the free run.
May combine two claims.
InterpretationreasoningHigh succinate concentration and elevated complex II activity suppress ROS generation from FAD but induce superoxide production at complex I due to RET.
“A high succinate concentration and elevated complex II activity will suppress ROS generation from FAD, but will induce superoxide production at complex I due to RET (Fig. 3A).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationDiazoxide and brief ischemic intervals during early reperfusion improve heart recovery and reduce infarct size, a phenomenon termed postconditioning.
“Diazoxide as well as several very brief ischemic intervals (10 s) during the early phase of reperfusion also improve the recovery of the heart and reduce infarct size, a phenomenon termed postconditioning [8].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] 8. A.P. Halestrap, S.J. Clarke, I. Khaliulin, The role of mitochondria in protection of the heart by preconditioning, Biochim. Biophys. Acta 1767 (2007) 1007-1031. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe Qo site of complex III has been considered a source for mitochondria-derived signaling ROS in several cellular processes including HIF-1α stabilization.
“This site has been considered as a source for mitochondria-derived 'signaling ROS' in several cellular processes including the stabilization of the hypoxia-inducible factor 1-α [135][136][137].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [135][136][137]
Not checked in the free run.
May combine two claims.
InterpretationcitationDiazoxide and ischemic preconditioning-associated ROS production is attenuated by myxothiazol, indicating that the Qo site of complex III is the source.
“Importantly, diazoxide and ischemic preconditioning associated ROS production is attenuated by myxothiazol [132,134], which clearly indicates that the Q o site of complex III is the source.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [132] 132. O. Oldenburg, M.V. Cohen, J.M. Downey, Mitochondrial K ATP channels in preconditioning, J. Mol. Cell. Cardiol. 35 (2003) 569-575. source
Not checked in the free run.
- cites [134] 134. T.L. Vanden Hoek, L.B. Becker, Z. Shao, C. Li, P.T. Schumacker, Reactive oxygen spe- cies released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes, J. Biol. Chem. 273 (1998) 18092-18098. source
Not checked in the free run.
May combine two claims.
InterpretationcitationIt seems plausible that uncouplers and complex I inhibitors protect by suppressing RET-induced superoxide production by complex I, though Chen et al. suggested complex III as the ROS source.
“It seems plausible that both substance groups exert their protective effects by suppressing the RET-induced superoxide production by complex I (Section 3.2), but Chen et al. suggested complex III as the source of ROS [123].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [123] 123. Q. Chen, A.K.S. Camara, D.F. Stowe, C.L. Hoppel, E.J. Lesnefsky, Modulation of electron transport protects cardiac mitochondria and decreases myocardial in- jury during ischemia and reperfusion, Am. J. Physiol. 292 (2007) C137-C147. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA prolonged period of ischemia followed by reperfusion irreversibly damages the heart and other tissues.
“It is well known that a prolonged period of ischemia followed by reperfusion irreversibly damages the heart and other tissues (overview in [8,9]).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [8] 8. A.P. Halestrap, S.J. Clarke, I. Khaliulin, The role of mitochondria in protection of the heart by preconditioning, Biochim. Biophys. Acta 1767 (2007) 1007-1031. source
Not checked in the free run.
- cites [9] 9. D.M. Yellon, D.J. Hausenloy, Mechanisms of disease: myocardial reperfusion in- jury, N. Engl. J. Med. 357 (2007) 1121-1135. source
Not checked in the free run.
May combine two claims.
PremisecitationDuring ischemia, only a small increase of ROS is detected, but a burst occurs upon reperfusion.
“During ischemia, only a small increase of ROS has been detected, but a burst occurs upon reperfusion [43,125].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [43] 43. P. Pasdois, B. Beauvoit, L. Tariosse, B. Vinassa, S. Bonoron-Adele, P. Dos Santos, Effect of diazoxide on flavoprotein oxidation and reactive oxygen species gener- ation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers, Am. J. Physiol. 294 (2008) H2088-H2097.
Not checked in the free run.
- cites [125] 125. L.G. Kevin, A.K.S. Camara, M.L. Riess, E. Novalija, D.F. Stowe, Ischemic preconditioning alters real-time measure of O 2 radicals in intact hearts with is- chemia and reperfusion, Am. J. Physiol. 284 (2003) H566-H574.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThere is general uncertainty whether applied concentrations in various test systems result in similar effective concentrations, influenced by partition coefficient and membrane permeability.
“However, there is general uncertainty whether the applied concentration in various test systems will result in similar effective concentrations, which might be largely influenced by the partition coefficient and relative membrane permeability of the applied drug.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.
Interpretationown dataDiazoxide probably binds to the Qp site of complex II and might directly induce ROS generation at FAD at relatively low succinate concentrations.
“Alternatively, diazoxide that probably binds to the Qp site of complex II (unpublished results) might directly induce ROS generation at the FAD at relatively low succinate concentrations (Fig. 3C).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites unpublished results
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationEffects of diazoxide on mitochondrial respiration occur at concentrations above those usually applied for mitoKATP opening.
“It has been pointed out that the effects of diazoxide on mitochondrial respiration occur at concentrations that are above the concentrations that are usually applied for mitoK ATP opening [151].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [151] 151. A.J. Kowaltowski, S. Seetharaman, P. Paucek, K.D. Garlid, Bioenergetic conse- quences of opening the ATP-sensitive K + channel of heart mitochondria, Am. J. Physiol. 280 (2001) H649-H657.
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningIt is uncertain whether this mechanism correctly describes ROS generation in vivo.
“Hence, it is uncertain whether this mechanism correctly describes ROS generation in vivo.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIt was concluded from many investigations that diazoxide targets mitoKATP and that this channel plays a central role in cardioprotection by ischemic and pharmacological preconditioning and by ischemic postconditioning.
“It was concluded from many investigations that diazoxide targets a mitochondrial form of ATP-dependent K + channels (mitoK ATP ) and that this channel plays a central role in cardioprotection by ischemic and pharmacological preconditioning and by ischemic postconditioning [140][141][142].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [140][141][142]
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe effect of atpenin A5 was independent of complex II inhibition, and the authors suggested opening of the putative mitoKATP channel as the mechanism.
“The effect of atpenin A5 was independent of complex II inhibition, and the authors suggested that opening of the putative mitoK ATP channel is the underlying mechanism.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] 44. A.P. Wojtovich, P.S. Brookes, The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial K-ATP channels, Basic Res. Cardiol. 104 (2009) 121-129. source
Not checked in the free run.
Probably not a substantial claim: may not pass S1 (asserted).
PremisecitationAn alternative hypothesis relates the cardioprotective effects of atpenins to modulation of mitochondrial ROS production.
“Hence, an alternative hypothesis was presented that relates the cardioprotective effects of atpenins to the modulation of mitochondrial ROS production [16].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] 16. S. Dröse, L. Bleier, U. Brandt, A common mechanism links differently acting com- plex II inhibitors to cardioprotection: modulation of mitochondrial reactive ox- ygen species production, Mol. Pharmacol. 79 (2011) 814-822. source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA model was presented that merges the two conflicting views, i.e., that complex II may be a component or regulator of the mitoKATP channel.
“Recently, a model was presented that merges these two conflicting views, i.e. that complex II may be a component or regulator of the mitoK ATP channel [44,156,157].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [44] 44. A.P. Wojtovich, P.S. Brookes, The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial K-ATP channels, Basic Res. Cardiol. 104 (2009) 121-129. source
Not checked in the free run.
- cites [156] 156. H. Ardehali, Z.H. Chen, Y. Ko, R. Mejia-Alvarez, E. Marban, Multiprotein complex containing succinate dehydrogenase confers mitochondrial ATP-sensitive K + channel activity, Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 11880-11885. source
Not checked in the free run.
- cites [157] 157. A.P. Wojtovich, P.S. Brookes, The endogenous mitochondrial complex II inhibitor malonate regulates mitochondrial ATP-sensitive potassium channels: implications for ischemic preconditioning, Biochim. Biophys. Acta 1777 (2008) 882-889. source
Not checked in the free run.
May combine two claims.
PremisecitationKATP channel subunits could not be identified in highly purified mitochondria, challenging the existence of mitoKATP.
“Especially, the fact that the K ATP channel subunits could not be identified so far in highly purified mitochondria challenges its existence [145,146].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [145] 145. T. Brustovetsky, N. Shalbuyeva, N. Brustovetsky, Lack of manifestations of diazoxide/5-hydroxydecanoatesensitive K ATP channel in rat brain nonsynaptosomal mitochondria, J. Physiol. Lond. 568 (2005) 47-59. source
Not checked in the free run.
- cites [146] 146. D.B. Foster, J.J. Rucker, E. Marban, Is Kir6.1 a subunit of mitoK ATP ? Biochem. Biophys. Res. Commun. 366 (2008) 649-656. source
Not checked in the free run.
May combine two claims.
PremisecitationDiazoxide inhibits complex II, while the KATP channel antagonist 5-HD can be metabolized by mitochondrial β-oxidation.
“Diazoxide inhibits complex II [128,129,147], while the K ATP channel antagonist 5-HD can be metabolized by the ß-oxidation pathway of the mitochondria [148][149][150].”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [128] 128. P.J. Hanley, M. Mickel, M. Löffler, U. Brandt, J. Daut, K ATP channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart, J. Physiol. 542 (2002) 735-741. source
Not checked in the free run.
- cites [129] 129. S. Dröse, U. Brandt, P.J. Hanley, K + -independent actions of diazoxide question the role of inner membrane K ATP channels in mitochondrial cytoprotective sig- naling, J. Biol. Chem. 281 (2006) 23733-23739. source
Not checked in the free run.
- cites [147] 147. S. Ovide-Bordeaux, R. Ventura-Clapier, V. Veksler, Do modulators of the mito- chondrial K ATP channel change the mitochondria in situ? J. Biol. Chem. 275 (2000) 37291-37295. source
Not checked in the free run.
- cites [148][149][150]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe existence of a mitoKATP channel is controversial.
“However, the existence of such a mitoK ATP channel is controversial [8,39,[142][143][144].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8,39,[142][143][144]
Not checked in the free run.
The paper relies on this without support.
The mechanisms of complex II-related ROS production observed in isolated mitochondria, submitochondrial particles, bacteria, and nematodes are representative of mammalian cardiac mitochondria relevant to ischemia/reperfusion and preconditioning.
“It is important to note that the overall structural and functional similarity of E. coli SQR and QFR to mammalian complex II has made them useful models systems for structure-function investigations and the analysis of disease-related human mutations [14].”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In sub-mitochondrial particles, CII can produce ROS upon Qp site inhibition only when FAD is reduced and the dicarboxylate site is unoccupied.
“In sub-mitochondrial particles, it has been previously established that CII can produce ROS upon Q p site inhibition only when FAD is reduced and the dicarboxylate site is unoccupied.7,38”
From Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation (2015) · cites this paper as [38]
Section 3.1 states that complex II generates ROS when FAD is reduced and the dicarboxylate site is unoccupied; the Conclusions say Qp-site inhibitors can promote ROS production from the flavin site. But the paper presents the occupancy-and-reduction mechanism as proposed, not established specifically in submitochondrial particles. Its discussion of the relevant mammalian experiments identifies isolated mitochondria as the preparation. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Cites
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084 · see citing works
Yellon, D. M., & Hausenloy, D. J. (2007) · New England Journal of Medicine · doi:10.1056/nejmra071667 · Cited by 3,797 · see citing works
Chandel, N. S., McClintock, D. S., Feliciano, C. E., Wood, T. M., Melendez, J. A., Rodriguez, A. M., & Schumacker, P. T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001914200 · Cited by 2,000 · see citing works
Production of Reactive Oxygen Species by Mitochondria
Chen, Q., Vazquez, E. J., Moghaddas, S., Hoppel, C. L., & Lesnefsky, E. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304854200 · Cited by 1,616 · see citing works
The cellular production of hydrogen peroxide
Boveris, A., Oshino, N., & Chance, B. (1972) · Biochemical Journal · doi:10.1042/bj1280617 · Cited by 1,549 · see citing works
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K. D., Simon, M. C., Hammerling, U., & Schumacker, P. T. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.001 · Cited by 1,545 · see citing works
Ying, W. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1672 · Cited by 1,494 · see citing works
Supercomplexes in the respiratory chains of yeast and mammalian mitochondria
Schägger, H., & Pfeiffer, K. (2000) · The EMBO Journal · doi:10.1093/emboj/19.8.1777 · Cited by 1,356 · see citing works
Generation of reactive oxygen species by the mitochondrial electron transport chain
Liu, Y., Fiskum, G., & Schubert, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00744.x · Cited by 1,260 · see citing works
Thiol chemistry and specificity in redox signaling
Winterbourn, C. C., & Hampton, M. B. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.05.004 · Cited by 1,226 · see citing works
The sites and topology of mitochondrial superoxide production
Brand, M. D. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.01.003 · Cited by 1,217 · see citing works
Mitochondria and reactive oxygen species
Kowaltowski, A. J., de Souza-Pinto, N. C., Castilho, R. F., & Vercesi, A. E. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.05.004 · Cited by 1,162 · see citing works
Preconditioning the myocardium: from cellular physiology to clinical cardiology
YELLON, D. M., & DOWNEY, J. M. (2003) · Physiological Reviews · doi:10.1152/physrev.00009.2003 · Cited by 1,062 · see citing works
Trends in oxidative aging theories
Muller, F. L., Lustgarten, M. S., Jang, Y., Richardson, A., & Van Remmen, H. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.03.034 · Cited by 1,053 · see citing works
Cardioprotective Effect of Diazoxide and Its Interaction With Mitochondrial ATP-Sensitive K+Channels
Garlid, K., Pauček, P., Yarov-Yarovoy, V. M., Murray, H. N., Darbenzio, R. B., DʼAlonzo, A. J., Lodge, N. J., Smith, M. A., & Grover, G. J. (1997) · Circulation Research · doi:10.1161/01.res.81.6.1072 · Cited by 1,019 · see citing works
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011 · see citing works
Architecture of succinate dehydrogenase and reactive oxygen species generation
Yankovskaya, V., Horsefield, R., Törnroth, S., Luna-Chavez, C., Miyoshi, H., Léger, C., Byrne, B., Cecchini, G., & Iwata, S. (2003) · Science · doi:10.1126/science.1079605 · Cited by 927 · see citing works
Crystal Structure of Mitochondrial Respiratory Membrane Protein Complex II
Sun, F., Huo, X., Zhai, Y., Wang, A., Xu, J., Su, D., Bartlam, M., & Rao, Z. (2005) · Cell · doi:10.1016/j.cell.2005.05.025 · Cited by 881 · see citing works
The role of mitochondria in reactive oxygen species metabolism and signaling
Starkov, A. A. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.015 · Cited by 846 · see citing works
Respiratory active mitochondrial supercomplexes
Acín-Pérez, R., Fernández-Silva, P., Peleato, M. L., Pérez-Martos, A., & Enriquez, J. A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.021 · Cited by 817 · see citing works
Vanden Hoek, T. L., Becker, L. B., Shao, Z., Li, C., & Schumacker, P. T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18092 · Cited by 721 · see citing works
New concepts in reactive oxygen species and cardiovascular reperfusion physiology
Becker, L. C. (2003) · Cardiovascular Research · doi:10.1016/j.cardiores.2003.10.025 · Cited by 703 · see citing works
Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species
Starkov, A. A., Fiskum, G. M., Chinopoulos, C., Lorenzo, B. J., Browne, S. E., Patel, M. S., & Beal, M. F. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1899-04.2004 · Cited by 692 · see citing works
A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes.
Ishii, N., Fujii, M., Hartman, P. S., Tsuda, M., Yasuda, K., Senoo-Matsuda, N., Yanase, S., Ayusawa, D., & Suzuki, K. (1998) · Nature · doi:10.1038/29331 · Cited by 687 · see citing works
Quinlan, C. L., Orr, A. L., Perevoshchikova, I. V., Treberg, J. R., Ackrell, B. A., & Brand, M. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.374629 · Cited by 670 · see citing works
The mitochondrial energy transduction system and the aging process
Navarro, A., & Boveris, A. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00213.2006 · Cited by 646 · see citing works
Votyakova, T. V., & Reynolds, I. J. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00548.x · Cited by 601 · see citing works
Function and Structure of Complex II of the Respiratory Chain
Cecchini, G. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161700 · Cited by 556 · see citing works
Jo, S.-H., Son, M.-K., Koh, H.-J., Lee, S.-M., Song, I.-H., Kim, Y.-O., Lee, Y.-S., Jeong, K.-S., Kim, W. B., Park, J.-W., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010120200 · Cited by 536 · see citing works
Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling
Cox, A. G., Winterbourn, C. C., & Hampton, M. B. (2009) · Biochemical Journal · doi:10.1042/bj20091541 · Cited by 530 · see citing works
Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain
Dröse, S., & Brandt, U. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3573-0_6 · Cited by 519 · see citing works
Self-citationRegulation of Succinate Dehydrogenase Activity by SIRT3 in Mammalian Mitochondria
Çimen, H., Han, M., Yang, Y., Tong, Q., Koc, H., & Koc, E. C. (2009) · Biochemistry · doi:10.1021/bi901627u · Cited by 478 · see citing works
LAMBERT, A. J., & BRAND, M. D. (2004) · Biochemical Journal · doi:10.1042/bj20040485 · Cited by 470 · see citing works
The Mitochondrial K Channel as a Receptor for Potassium Channel Openers
Garlid, K., Pauček, P., Yarov-Yarovoy, V. M., Sun, X., & Schindler, P. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8796 · Cited by 445 · see citing works
Evidence for Mitochondrial K + Channels and Their Role in Cardioprotection
O'Rourke, B. P. (2004) · Circulation Research · doi:10.1161/01.res.0000117583.66950.43 · Cited by 444 · see citing works
Succinate: quinone oxidoreductases
Hägerhäll, C. (1997) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(97)00019-4 · Cited by 439 · see citing works
Structure of the Escherichia coli Fumarate Reductase Respiratory Complex
Iverson, T. M., Luna-Chavez, C., Cecchini, G., & Rees, D. C. (1999) · Science · doi:10.1126/science.284.5422.1961 · Cited by 416 · see citing works
Bardella, C., Pollard, P. J., & Tomlinson, I. (2011) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2011.07.003 · Cited by 395 · see citing works
Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism
Forbes, R. A., Steenbergen, C., & Murphy, E. (2001) · Circulation Research · doi:10.1161/hh0801.089342 · Cited by 395 · see citing works
The role of mitochondria in protection of the heart by preconditioning
Halestrap, A. P., Clarke, S. J., & Khaliulin, I. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.05.008 · Cited by 390 · see citing works
The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex
Dröse, S., & Brandt, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803236200 · Cited by 386 · see citing works
Self-citationAlston, T. A., Mela, L., & Bright, H. J. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.9.3767 · Cited by 380 · see citing works
Generation of superoxide by the mitochondrial Complex I
Grivennikova, V. G., & Vinogradov, A. D. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.013 · Cited by 379 · see citing works
Superoxide generation by complex III: From mechanistic rationales to functional consequences
Bleier, L., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.12.002 · Cited by 369 · see citing works
Self-citationSuccinate Dehydrogenase Is a Direct Target of Sirtuin 3 Deacetylase Activity
Finley, L. W. S., Haas, W., Desquiret‐Dumas, V., Wallace, D. C., Procaccio, V., Gygi, S. P., & Haigis, M. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023295 · Cited by 364 · see citing works
Respiratory chain supercomplexes of mitochondria and bacteria
Schägger, H. (2002) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(02)00271-2 · Cited by 363 · see citing works
The role of the mitochondrial permeability transition pore in heart disease
Halestrap, A. P., & Pasdois, P. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.12.017 · Cited by 362 · see citing works
Bioenergetic consequences of opening the ATP-sensitive K+channel of heart mitochondria
Kowaltowski, A. J., Seetharaman, S., Pauček, P., & Garlid, K. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.2.h649 · Cited by 351 · see citing works
Structure of fumarate reductase from Wolinella succinogenes at 2.2 Å resolution
Lancaster, C. R. D., Kröger, A., Auer, M., & Michel, H. (1999) · Nature · doi:10.1038/46483 · Cited by 339 · see citing works
K<sub>ATP</sub> channel‐independent targets of diazoxide and 5‐hydroxydecanoate in the heart
Hanley, P. J., Mickel, M., Löffler, M., Brandt, U., & Daut, J. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.023960 · Cited by 320 · see citing works
Weinberg, J. M., Venkatachalam, M. A., Roeser, N. F., & Nissim, I. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2826 · Cited by 317 · see citing works
Messner, K. R., & Imlay, J. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204958200 · Cited by 301 · see citing works
Superoxide Is Produced by the Reduced Flavin in Mitochondrial Complex I
Pryde, K. R., & Hirst, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.186841 · Cited by 301 · see citing works
Dong, L.-F., Low, P., Dyason, J. C., Wang, X.-F., Procházka, L., Witting, P. K., Freeman, R., Swettenham, E., Vališ, K., Liu, J., et al. (2008) · Oncogene · doi:10.1038/onc.2008.69 · Cited by 297 · see citing works
Horsefield, R., Yankovskaya, V., Sexton, G., Whittingham, W., Shiomi, K., Ōmura, S., Byrne, B., Cecchini, G., & Iwata, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508173200 · Cited by 292 · see citing works
Heide, H., Bleier, L., Steger, M., Ackermann, J., Dröse, S., Schwamb, B., Zörnig, M., Reichert, A. S., Koch, I., Wittig, I., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.009 · Cited by 273 · see citing works
Self-citationKevin, L. G., Camara, A. K. S., Riess, M. L., Novalija, E., & Stowe, D. F. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00711.2002 · Cited by 272 · see citing works
Chen, Q., Camara, A. K. S., Stowe, D. F., Hoppel, C. L., & Lesnefsky, E. J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00270.2006 · Cited by 271 · see citing works
Senoo-Matsuda, N., Yasuda, K., Tsuda, M., Ohkubo, T., Yoshimura, S., Nakazawa, H., Hartman, P. S., & Ishii, N. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104718200 · Cited by 271 · see citing works
Miyadera, H., Shiomi, K., Ui, H., Yamaguchi, Y., Masuma, R., Tomoda, H., Miyoshi, H., Osanai, A., Kita, K., & Ōmura, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0237315100 · Cited by 256 · see citing works
Mitochondrial NADPH, transhydrogenase and disease
Rydström, J. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.03.010 · Cited by 256 · see citing works
[47] Mammalian succinate dehydrogenase
Ackrell, B. A. C., Kearney, E. B., & Singer, T. P. (1978) · Methods in Enzymology · doi:10.1016/s0076-6879(78)53050-4 · Cited by 255 · see citing works
Lim, K. H. H., Javadov, S. A., Das, M., Clarke, S. J., Suleiman, M. S., & Halestrap, A. P. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.031484 · Cited by 219 · see citing works
HANLEY, P., & DAUT, J. (2005) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2005.04.002 · Cited by 218 · see citing works
Ardehali, H., Chen, Z., Ko, Y., Mejía-Alvarez, R., & Marbán, E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401703101 · Cited by 215 · see citing works
Treberg, J. R., Quinlan, C. L., & Brand, M. D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.252502 · Cited by 212 · see citing works
Sazanov, L. A., & Jackson, J. B. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00370-x · Cited by 205 · see citing works
Dong, L.-F., Jameson, V. J. A., Tilly, D., Cerny, J., Mahdavian, E., Marín-Hernández, A., Hernández-Esquivel, L., Rodríguez-Enríquez, S., Stursa, J., Witting, P. K., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.186643 · Cited by 200 · see citing works
The mechanism of superoxide production by the antimycin-inhibited mitochondrial Q-cycle
Quinlan, C. L., Gerencser, A. A., Treberg, J. R., & Brand, M. D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.267898 · Cited by 200 · see citing works
Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/peroxiredoxin system
Drechsel, D. A., & Patel, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.101196 · Cited by 199 · see citing works
Stanley, B. A., Sivakumaran, V., Shi, S., McDonald, I., Lloyd, D., Watson, W. H., Aon, M. A., & Paolocci, N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.284612 · Cited by 197 · see citing works
Özcan, C., Bienengraeber, M., Dzeja, P. P., & Terzic, A. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00552.2001 · Cited by 195 · see citing works
Folbergrová, J., Ljunggren, B., Norberg, K. A., & Siesjö, B. K. (1974) · Brain Research · doi:10.1016/0006-8993(74)90690-8 · Cited by 192 · see citing works
Kinetic Study of the Dicarboxylate Carrier in Rat Liver Mitochondria
Palmieri, F., Prezioso, G., Quagliariello, E., & Klingenberg, M. (1971) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1971.tb01515.x · Cited by 189 · see citing works
Garcia, J., Han, D., Sancheti, H., Yap, L.-P., Kaplowitz, N., & Cadenas, E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.164160 · Cited by 178 · see citing works
Ksenzenko, M. Y., Konstantinov, A. A., Khomutov, G. B., Tikhonov, A. N., & Ruuge, E. K. (1983) · FEBS Letters · doi:10.1016/0014-5793(83)80200-2 · Cited by 160 · see citing works
Muller, F. L., Liu, Y., Abdul-Ghani, M. A., Lustgarten, M. S., Bhattacharya, A., Jang, Y. C., & Van Remmen, H. (2008) · Biochemical Journal · doi:10.1042/bj20071162 · Cited by 150 · see citing works
Cardioprotection by metabolic shut-down and gradual wake-up
Burwell, L. S., Nadtochiy, S. M., & Brookes, P. S. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.02.026 · Cited by 146 · see citing works
Maklashina, E., Berthold, D. A., & Cecchini, G. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.22.5989-5996.1998 · Cited by 144 · see citing works
Ferranti, R., da Silva, M. M., & Kowaltowski, A. J. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00007-3 · Cited by 136 · see citing works
Respiration-dependent Removal of Exogenous H2O2 in Brain Mitochondria
Zoccarato, F., Cavallini, L., & Alexandre, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308143200 · Cited by 130 · see citing works
Ralph, S. J., Moreno-Sánchez, R., Neuzil, J., & Rodríguez-Enríquez, S. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0566-7 · Cited by 126 · see citing works
Wojtovich, A. P., & Brookes, P. S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.03.025 · Cited by 119 · see citing works
Lenaz, G., & Genova, M. L. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3573-0_5 · Cited by 114 · see citing works
Wojtovich, A. P., & Brookes, P. S. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0001-y · Cited by 107 · see citing works
Dong, L., Jameson, V. J. A., Tilly, D., Procházka, L., Rohlena, J., Vališ, K., Truksa, J., Zobalová, R., Mahdavian, E., Kľučková, K., et al. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.02.032 · Cited by 105 · see citing works
Dröse, S., Brandt, U., & Hanley, P. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602570200 · Cited by 105 · see citing works
Self-citationSzeto, S. S. W., Reinke, S. N., Sykes, B. D., & Lemire, B. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700601200 · Cited by 104 · see citing works
Targeting nucleotide-requiring enzymes: implications for diazoxide-induced cardioprotection
Dzeja, P. P., Bast, P., Özcan, C., Valverde, A. M., Holmuhamedov, E., Wylen, D. G. L. V., & Terzic, A. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00847.2002 · Cited by 104 · see citing works
Mitochondrial complex II, a novel target for anti-cancer agents
Kluckova, K., Bezawork-Geleta, A., Rohlena, J., Dong, L., & Neuzil, J. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.10.015 · Cited by 104 · see citing works
Guo, J., & Lemire, B. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306312200 · Cited by 103 · see citing works
Role of Oxalacetate in the Regulation of Mammalian Succinate Dehydrogenase
Ackrell, B. A. C., Kearney, E. B., & Mayr, M. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42790-7 · Cited by 102 · see citing works
Moreno‐Sánchez, R., Hernández‐Esquivel, L., Rivero‐Segura, N. A., Marín‐Hernández, A., Neuzil, J., Ralph, S. J., & Rodríguez‐Enríquez, S. (2013) · The FEBS Journal · doi:10.1111/febs.12086 · Cited by 100 · see citing works
Ischemia and the aging brain — studies on glucose and energy-metabolism in rat cerebral-cortex
Hoyer, S., & Krier, C. (1986) · Neurobiology of Aging · doi:10.1016/0197-4580(86)90022-9 · Cited by 98 · see citing works
Control of succinate dehydrogenase in mitochondria
Gutman, M., Kearney, E. B., & Singer, T. P. (1971) · Biochemistry · doi:10.1021/bi00801a025 · Cited by 97 · see citing works
Mitochondrial KATP channels in preconditioning
Oldenburg, O. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00115-9 · Cited by 94 · see citing works
Role of reactive oxygen species in the induction of apoptosis by α‐tocopheryl succinate
Kang, Y., Lee, E., Choi, M., Ku, J., Kim, S. H., Park, Y., & Lim, S. (2004) · International Journal of Cancer · doi:10.1002/ijc.20424 · Cited by 92 · see citing works
Salerno, J. C., & Ohnishi, T. (1980) · Biochemical Journal · doi:10.1042/bj1920769 · Cited by 90 · see citing works
Ruprecht, J. J., Yankovskaya, V., Maklashina, E., Iwata, S., & Cecchini, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.010058 · Cited by 90 · see citing works
Potassium channel openers are uncoupling protonophores: implication in cardioprotection
Holmuhamedov, E. L., Jahangir, A., Oberlin, A., Komarov, A., Colombini, M., & Terzic, A. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.05.031 · Cited by 90 · see citing works
Malińska, D., Kulawiak, B., Kudin, A. P., Kovacs, R., Huchzermeyer, C., Kann, O., Szewczyk, A. M., & Kunz, W. S. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.03.001 · Cited by 90 · see citing works
Ohnishi, T., King, T. E., Salerno, J. C., Blum, H., Bowyer, J. R., & Maida, T. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69241-0 · Cited by 88 · see citing works
Hanley, P. J., Dröse, S., Brandt, U., Lareau, R. A., Banerjee, A. L., Srivastava, D. K., Banaszak, L. J., Barycki, J. J., Veldhoven, P. P. V., & Daut, J. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.073932 · Cited by 88 · see citing works
Self-citationHanley, P. J., Gopalan, K. V., Lareau, R. A., Srivastava, D. K., von Meltzer, M., & Daut, J. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.037044 · Cited by 88 · see citing works
Cytopathies involving mitochondrial complex II
Ackrell, B. A. C. (2002) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(02)00012-2 · Cited by 86 · see citing works
Treberg, J. R., Quinlan, C. L., & Brand, M. D. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07693.x · Cited by 85 · see citing works
The mitochondrial KATP channel—Fact or fiction?
Garlid, K., & Halestrap, A. P. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2011.12.011 · Cited by 85 · see citing works
Diazoxide, an inhibitor of succinate oxidation
S, G., W., C. R., Porten, R., & Boj, D. (1969) · Biochemical Pharmacology · doi:10.1016/0006-2952(69)90200-7 · Cited by 84 · see citing works
The quinone-binding and catalytic site of complex II
Maklashina, E., & Cecchini, G. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.015 · Cited by 82 · see citing works
Brockmann, K., Bjornstad, A., Dechent, P., Korenke, C. G., Smeitink, J., Trijbels, J. M. F., Athanassopoulos, S., Villagran, R., Skjeldal, O. H., Wilichowski, E., et al. (2002) · Annals of Neurology · doi:10.1002/ana.10232 · Cited by 81 · see citing works
Catalytic mechanisms of complex II enzymes: A structural perspective
Iverson, T. M. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.09.008 · Cited by 80 · see citing works
Trumpower, B. L., & Simmons, Z. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)30054-6 · Cited by 77 · see citing works
Facundo, H. T. F., Carreira, R. S., de Paula, J. G., Santos, C. C. X., Ferranti, R., Laurindo, F. R. M., & Kowaltowski, A. J. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.08.041 · Cited by 72 · see citing works
Dröse, S., Hanley, P. J., & Brandt, U. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.01.011 · Cited by 72 · see citing works
Self-citationIs Kir6.1 a subunit of mitoKATP?
Brian Foster, D., Rucker, J. J., & Marbán, E. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.11.154 · Cited by 71 · see citing works
Hohl, C., Oestreich, R., Rösen, P., Wiesner, R., & Grieshaber, M. (1987) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(87)90519-4 · Cited by 68 · see citing works
Zoccarato, F., Cavallini, L., Bortolami, S., & Alexandre, A. (2007) · Biochemical Journal · doi:10.1042/bj20070215 · Cited by 66 · see citing works
Tran, Q. M., Rothery, R. A., Maklashina, E., Cecchini, G., & Weiner, J. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607476200 · Cited by 64 · see citing works
Dröse, S., Bleier, L., & Brandt, U. (2011) · Molecular Pharmacology · doi:10.1124/mol.110.070342 · Cited by 64 · see citing works
Self-citationDo Modulators of the Mitochondrial KATP Channel Change the Function of Mitochondria in Situ?
Ovide-Bordeaux, S., Ventura-Clapier, R., & Veksler, V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005772200 · Cited by 60 · see citing works
Glutamate degradation in the ischemic dog heart — contribution to anaerobic energy-production
Wiesner, R. (1989) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(89)91492-2 · Cited by 59 · see citing works
Maklashina, E., Iverson, T. M., Sher, Y. I., Kotlyar, V., Andréll, J., Mirza, O., Hudson, J. M., Armstrong, F. A., Rothery, R. A., Weiner, J. H., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512544200 · Cited by 58 · see citing works
Riess, M. L., Camara, A. K. S., Heinen, A., Eells, J. T., Henry, M. M., & Stowe, D. F. (2008) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31816bf4a4 · Cited by 57 · see citing works
Model animals for the study of oxidative stress from complex II
Ishii, T., Miyazawa, M., Onouchi, H., Yasuda, K., Hartman, P. S., & Ishii, N. (2012) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.10.016 · Cited by 57 · see citing works
Structural basis for malfunction in complex II
Iverson, T. M., Maklashina, E., & Cecchini, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r112.408419 · Cited by 53 · see citing works
Inhibition of mitochondrial metabolism by the diabetogenic thiadiazine diazoxide—I
Schäfer, G., Portenhauser, R., & Trolp, R. (1971) · Biochemical Pharmacology · doi:10.1016/0006-2952(71)90358-3 · Cited by 52 · see citing works
Owens, K. M., Aykin‐Burns, N., Dayal, D., Coleman, M. C., Domann, F. E., & Spitz, D. R. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.435 · Cited by 52 · see citing works
<i>Escherichia coli</i> succinate dehydrogenase variant lacking the heme <i>b</i>
Tran, Q. M., Rothery, R. A., Maklashina, E., Cecchini, G., & Weiner, J. H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707732104 · Cited by 51 · see citing works
Differences in Protonation of Ubiquinone and Menaquinone in Fumarate Reductase from Escherichia coli
Maklashina, E., Hellwig, P., Rothery, R. A., Kotlyar, V., Sher, Y. I., Weiner, J. H., & Cecchini, G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602938200 · Cited by 50 · see citing works
Tightly bound oxalacetate and the activation of succinate dehydrogenase
Kearney, E. B., Ackrell, B. A. C., & Mayr, M. (1972) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(72)90328-2 · Cited by 50 · see citing works
Minners, J., Lacerda, L., Yellon, D. M., Opie, L. H., McLeod, C. J., & Sack, M. N. (2006) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-9066-6 · Cited by 49 · see citing works
Pasdois, P., Beauvoit, B. P., Tariosse, L., Jaspard‐Vinassa, B., Bonoron‐Adèle, S., & Santos, P. D. D. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01345.2007 · Cited by 48 · see citing works
Reaction site of carboxanilides and of thenoyltrifluoroacetone in complex II.
Ramsay, R. R., Ackrell, B. A. C., Coles, C. J., Singer, T. P., White, G. A., & Thorn, G. D. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.2.825 · Cited by 47 · see citing works
Brustovetsky, T., Shalbuyeva, N., & Brustovetsky, N. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.091199 · Cited by 46 · see citing works
Ishii, T., Miyazawa, M., Onodera, A., Yasuda, K., Kawabe, N., Kirinashizawa, M., Yoshimura, S., Maruyama, N., Hartman, P. S., & Ishii, N. (2011) · Mitochondrion · doi:10.1016/j.mito.2010.09.006 · Cited by 42 · see citing works
Wiesner, R. J., Rösen, P., & Grieshaber, M. K. (1988) · Biochemical Medicine and Metabolic Biology · doi:10.1016/0885-4505(88)90100-4 · Cited by 42 · see citing works
Carboxins: Powerful selective inhibitors of succinate oxidation in animal tissues
Mowery, P. C., Ackrell, B. A. C., Singer, T. P., White, G. A., & Thorn, G. D. (1976) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(76)90290-4 · Cited by 42 · see citing works
Adebiyi, A., McNally, E. M., & Jaggar, J. H. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.048165 · Cited by 42 · see citing works
Erecińska, M., & Wilson, D. F. (1976) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(76)90333-7 · Cited by 41 · see citing works
Paranagama, M. P., Sakamoto, K., Amino, H., Awano, M., Miyoshi, H., & Kita, K. (2010) · Mitochondrion · doi:10.1016/j.mito.2009.12.145 · Cited by 40 · see citing works
Influence of some biological pyrimidines on the succinate cycle during and after cerebral ischemia
Benzi, G. M., Arrigoni, E., Marzatico, F., & Villa, R. F. (1979) · Biochemical Pharmacology · doi:10.1016/0006-2952(79)90024-8 · Cited by 38 · see citing works
Maklashina, E., Kotlyar, A. B., Karliner, J. S., & Cecchini, G. (2004) · FEBS Letters · doi:10.1016/s0014-5793(03)01369-3 · Cited by 37 · see citing works
Zoccarato, F., Cavallini, L., & Alexandre, A. (2009) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-009-9238-2 · Cited by 31 · see citing works
Oestreicher, A. B., van den Bergh, S. G., & Slater, E. C. (1969) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(69)90192-3 · Cited by 29 · see citing works
Ksenzenko, M. Y., Konstantinov, A. A., Khomutov, G. B., Tikhonov, A. N., & Ruuge, E. K. (1984) · FEBS Letters · doi:10.1016/0014-5793(84)80579-7 · Cited by 25 · see citing works
Oxidation of malate by the mitochondrial succinate–ubiquinone reductase
Belikova, Y. O., Kotlyar, A. B., & Vinogradov, A. D. (1988) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(88)90245-9 · Cited by 23 · see citing works
Özcan, C., Terzic, A., & Bienengraeber, M. (2007) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31812378df · Cited by 23 · see citing works
Mitochondrial ATP-sensitive K+channels, protectors of the heart
Yamada, M. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2009.179028 · Cited by 21 · see citing works
Liu, B., Zhu, X., Chen, C., Hu, K., Swartz, H. M., Chen, Y., & He, G. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0283-2 · Cited by 21 · see citing works
Kopustinskienė, D. M., Liobikas, J., Škėmienė, K., Malinauskas, F., & Toleikis, A. (2010) · Cellular Physiology and Biochemistry · doi:10.1159/000276552 · Cited by 20 · see citing works
Long chain fatty acyl-CoA modulation of H2O2 release at mitochondrial complex I
Bortolami, S., Comelato, E., Zoccarato, F., Alexandre, A., & Cavallini, L. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9126-1 · Cited by 13 · see citing works
Selby, T. P., Hughes, K. A., Rauh, J. J., & Hanna, W. S. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.01.066 · Cited by 13 · see citing works
Out of plane distortions of the heme b of Escherichia coli succinate dehydrogenase
Tran, Q. M., Fong, C., Rothery, R. A., Maklashina, E., Cecchini, G., & Weiner, J. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032641 · Cited by 12 · see citing works
Huang, L.-S., Sun, G., Cobessi, D., Wang, A. C., Shen, J. T., Tung, E. Y., Anderson, V. E., & Berry, E. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511270200 · Cited by 10 · see citing works
The control of mitochondrial succinate-dependent H2O2 production
Zoccarato, F., Miotto, C., Cavallini, L., & Alexandre, A. (2011) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-011-9363-6 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 158 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kalogeris, T. J., Bao, Y., & Korthuis, R. J. (2014) · Redox Biology · doi:10.1016/j.redox.2014.05.006 · Cited by 719 · see citing works
Free Radical Properties, Source and Targets, Antioxidant Consumption and Health
Martemucci, G., Costagliola, C., Mariano, M., D’Andrea, L., Napolitano, P., & D‘Alessandro, A. G. (2022) · Oxygen · doi:10.3390/oxygen2020006 · Cited by 781 · see citing works
Mitochondrial composition and function under the control of hypoxia
Fuhrmann, D. C., & Brüne, B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.012 · Cited by 646 · see citing works
Functions of ROS in Macrophages and Antimicrobial Immunity
Herb, M., & Schramm, M. (2021) · Antioxidants · doi:10.3390/antiox10020313 · Cited by 633 · see citing works
Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis.
Tretter, L., Patócs, A., & Chinopoulos, C. (2016) · Biochimica et Biophysica Acta · doi:10.1016/j.bbabio.2016.03.012 · Cited by 502 · see citing works
Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment
Golpich, M., Amini, E., Mohamed, Z., Raymond, A. A., Ibrahim, N. M., & Ahmadiani, A. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12655 · Cited by 540 · see citing works
Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury
Fakhruddin, S., Alanazi, W. A., & Jackson, K. E. (2017) · Journal of Diabetes Research · doi:10.1155/2017/8379327 · Cited by 295 · see citing works
Contribution of metabolic reprogramming to macrophage plasticity and function
Kasmi, K. C. E., & Stenmark, K. R. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.09.001 · Cited by 276 · see citing works
Chen, R., Lai, U. H., Zhu, L., Singh, A., AlKataan, M. A. A., & Forsyth, N. R. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00132 · Cited by 271 · see citing works
Mechanism of antineoplastic activity of lonidamine
Nath, K., Guo, L., Nancolas, B., NELSON, D. S., Shestov, A. A., Lee, S., Roman, J., Zhou, R., Leeper, D. B., Halestrap, A. P., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.08.001 · Cited by 213 · see citing works
Suppressors of superoxide production from mitochondrial complex III
Orr, A. L., Vargas, L., Turk, C. N., Baaten, J., Matzen, J., Dardov, V. J., Attle, S. J., Li, J., Quackenbush, D., Goncalves, R. L. S., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1910 · Cited by 207 · see citing works
Generator-specific targets of mitochondrial reactive oxygen species
Bleier, L., Wittig, I., Heide, H., Steger, M., Brandt, U., & Dröse, S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.511 · Cited by 183 · see citing works
Self-citationInsights into the respiratory chain and oxidative stress
Larosa, V., & Remacle, C. (2018) · Bioscience Reports · doi:10.1042/bsr20171492 · Cited by 183 · see citing works
Inhibition of Mitochondrial Complex II by the Anticancer Agent Lonidamine
Guo, L., Shestov, A. A., Worth, A. J., Nath, K., NELSON, D. S., Leeper, D. B., Glickson, J. D., & Blair, I. A. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.697516 · Cited by 181 · see citing works
Roca, F. J., Whitworth, L. J., Prag, H. A., Murphy, M. P., & Ramakrishnan, L. (2022) · Science · doi:10.1126/science.abh2841 · Cited by 177 · see citing works
Mitochondrial complex II and reactive oxygen species in disease and therapy
Vanova, K. H., Kraus, M., Neužil, J., & Rohlena, J. (2020) · Redox Report · doi:10.1080/13510002.2020.1752002 · Cited by 162 · see citing works
Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation
Dröse, S., Brandt, U., & Wittig, I. (2014) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2014.02.006 · Cited by 153 · see citing works
Self-citationControlling Redox Status for Stem Cell Survival, Expansion, and Differentiation
Sart, S., Song, L., & Li, Y. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/105135 · Cited by 143 · see citing works
Ischemic A/D transition of mitochondrial complex I and its role in ROS generation
Dröse, S., Степанова, А., & Galkin, A. S. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.12.013 · Cited by 137 · see citing works
Self-citationSiebels, I., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.06.005 · Cited by 130 · see citing works
Self-citationGuerra‐Castellano, A., Dı́az-Quintana, A., Pérez‐Mejías, G., Elena‐Real, C. A., González‐Arzola, K., García‐Mauriño, S. M., la Rosa, M. Á. D., & Díaz‐Moreno, I. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1806833115 · Cited by 105 · see citing works
Cysteine-mediated redox signalling in the mitochondria
Bak, D. W., & Weerapana, E. (2014) · Molecular BioSystems · doi:10.1039/c4mb00571f · Cited by 100 · see citing works
Machine perfusion of the liver and bioengineering
Schlegel, A. A., Mergental, H., Fondevila, C., Porte, R. J., Friend, P. J., & Dutkowski, P. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.02.009 · Cited by 99 · see citing works
Guzzo, G., Sciacovelli, M., Bernardi, P., & Rasola, A. (2014) · Oncotarget · doi:10.18632/oncotarget.2472 · Cited by 97 · see citing works
Leishmania parasites exchange drug-resistance genes through extracellular vesicles
Douanne, N., Dong, G., Amin, A. B., Bernardo, L., Blanchette, M., Langlais, D., Olivier, M., & Fernandez‐Prada, C. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111121 · Cited by 92 · see citing works
The mitochondrial permeability transition pore and its adaptive responses in tumor cells
Rasola, A., & Bernardi, P. (2014) · Cell Calcium · doi:10.1016/j.ceca.2014.10.003 · Cited by 91 · see citing works
Florido, J., Martínez-Ruiz, L., Rodríguez-Santana, C., López‐Rodríguez, A., Hidalgo‐Gutiérrez, A., Cottet‐Rousselle, C., Lamarche, F., Schlattner, U., Guerra‐Librero, A., Aranda‐Martínez, P., et al. (2022) · Journal of Pineal Research · doi:10.1111/jpi.12824 · Cited by 84 · see citing works
Zhang, W., & Lang, R. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1266973 · Cited by 78 · see citing works
Modica-Napolitano, J. S., & Weissig, V. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160817394 · Cited by 80 · see citing works
Souders, C. L., Liang, X., Wang, X., Ector, N., Zhao, Y. H., & Martyniuk, C. J. (2018) · Aquatic Toxicology · doi:10.1016/j.aquatox.2018.03.031 · Cited by 74 · see citing works
Kuksal, N., Chalker, J., & Mailloux, R. J. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0160 · Cited by 74 · see citing works
Hardonnière, K., Saunier, E. F., Lemarié, A., Fernier, M., Gallais, I., Héliès‐Toussaint, C., Mograbi, B., Antonio, S., Bénit, P., Rustin, P., et al. (2016) · Scientific Reports · doi:10.1038/srep30776 · Cited by 72 · see citing works
Madungwe, N. B., Zilberstein, N., Feng, Y., & Bopassa, J. C. (2016) · PubMed Central · Cited by 71 · see citing works
Min, H., Jang, H.-J., Park, K. H., Hyun, S. Y., Park, S. J., Kim, J. H., Son, J., Kang, S. S., & Lee, H. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2041-z · Cited by 73 · see citing works
Kluckova, K., Sticha, M., Cerny, J., Mracek, T., Dong, L., Drahota, Z., Gottlieb, E., Neuzil, J., & Rohlena, J. (2015) · Cell Death & Disease · doi:10.1038/cddis.2015.110 · Cited by 66 · see citing works
“In sub-mitochondrial particles, it has been previously established that CII can produce ROS upon Qp site inhibition only when FAD is reduced and the dicarboxylate site is unoccupied.(7,38) In intact cells, this introduces an additional level of complexity, because the lack of enzymatically active CII will result in th…”
BackgroundMailloux, R. J. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102044 · Cited by 69 · see citing works
Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma
Zhang, L., Cao, Y., Guo, X., Wang, X., Han, X., Kanwore, K., Hong, X., Zhou, H., & Gao, D. (2023) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b2200269 · Cited by 68 · see citing works
The impact of age-related dysregulation of the angiotensin system on mitochondrial redox balance
Vajapey, R. S., Rini, D. A., Walston, J. D., & Abadir, P. M. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00439 · Cited by 69 · see citing works
Zhu, H., Tamura, T., Fujisawa, A., Nishikawa, Y., Cheng, R., Takato, M., & Hamachi, I. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c02547 · Cited by 67 · see citing works
Park, S. ‐., Kwon, O. S., Andtbacka, R. H. I., Hyngstrom, J. R., Reese, V. R., Murphy, M. P., & Richardson, R. S. (2017) · Acta Physiologica · doi:10.1111/apha.12893 · Cited by 67 · see citing works
Radiation-Induced Alterations in Mitochondria of the Rat Heart
Sridharan, V., Aykin‐Burns, N., Tripathi, P., Krager, K. J., Sharma, S., Moros, E. G., Corry, P. M., Nowak, G., Hauer‐Jensen, M., & Boerma, M. (2014) · Radiation Research · doi:10.1667/rr13452.1 · Cited by 65 · see citing works
Hu, C., Zhao, L., Peng, C., & Li, L. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13835 · Cited by 64 · see citing works
Kim, Y., Baek, J., Kim, S. H., Kim, M.-A., Lee, B., Ryu, N., Kim, K., Choi, D.-G., Kim, H.-M., Murphy, M. P., et al. (2018) · Redox Biology · doi:10.1016/j.redox.2018.11.013 · Cited by 64 · see citing works
Kôrge, P., John, S., Calmettes, G., & Weiss, J. N. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.768325 · Cited by 63 · see citing works
A paradoxical role of reactive oxygen species in cancer signaling pathway: Physiology and pathology
Ramalingam, V., & Rajaram, R. (2020) · Process Biochemistry · doi:10.1016/j.procbio.2020.09.032 · Cited by 60 · see citing works
Keshtzar, E., Khodayar, M. J., Javadipour, M., Ghaffari, M., Bolduc, D., & Rezaei, M. (2015) · Human & Experimental Toxicology · doi:10.1177/0960327115618247 · Cited by 61 · see citing works
Fuhrmann, D. C., Wittig, I., & Brüne, B. (2018) · Redox Biology · doi:10.1016/j.redox.2018.10.007 · Cited by 61 · see citing works
MDH2 produced OAA is a metabolic switch rewiring the fuelling of respiratory chain and TCA cycle
Molinié, T., Cougouilles, E., David, C., Cahoreau, E., Portais, J., & Mourier, A. (2022) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2022.148532 · Cited by 58 · see citing works
Степанова, А., Shurubor, Y. I., Valsecchi, F., Manfredi, G., & Galkin, A. S. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.06.002 · Cited by 57 · see citing works
Redox signaling in heart failure and therapeutic implications
Weissman, D., & Maack, C. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.05.013 · Cited by 59 · see citing works
Aerobic respiration: proof of concept for the oxygen-centric murburn perspective
Manoj, K. M., Parashar, A., Jacob, V. D., & Ramasamy, S. (2018) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2018.1552896 · Cited by 59 · see citing works
Surprisingly long survival of premature conclusions about naked mole‐rat biology
Braude, S. H., Holtze, S., Begall, S., Brenmoehl, J., Burda, H., Dammann, P., del Marmol, D., Gorshkova, E. A., Henning, Y., Hoeflich, A., et al. (2020) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12660 · Cited by 55 · see citing works
Genetic, epigenetic and biochemical regulation of succinate dehydrogenase function
Moosavi, B., Zhu, X., Yang, W., & Yang, G. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0264 · Cited by 57 · see citing works
Respiratory complex II: ROS production and the kinetics of ubiquinone reduction
Grivennikova, V. G., Kozlovsky, V. S., & Vinogradov, A. D. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.10.008 · Cited by 54 · see citing works
Cobley, J. N. (2020) · Antioxidants · doi:10.3390/antiox9100933 · Cited by 56 · see citing works
Gómez-Gallardo, M., Pérez‐Gallardo, R. V., Sánchez, L. A., Díaz-Pérez, A. L., Cortés‐Rojo, C., Meza‐Carmen, V., Saavedra‐Molina, A., Lara‐Romero, J., Jiménez‐Sandoval, S., Rodríguez, F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111585 · Cited by 54 · see citing works
Redox control of non-shivering thermogenesis
Lettieri‐Barbato, D. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.04.002 · Cited by 50 · see citing works
Степанова, А., Konràd, C., Manfredi, G., Springett, R., Ten, V. S., & Galkin, A. S. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14654 · Cited by 50 · see citing works
Okuda, J., Niizuma, S., Shioi, T., Kato, T., Inuzuka, Y., Kawashima, T., Tamaki, Y., Kawamoto, A., Tanada, Y., Iwanaga, Y., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072173 · Cited by 49 · see citing works
Shirakawa, R., Yokota, T., Nakajima, T., Takada, S., Yamane, M., Furihata, T., Maekawa, S., Nambu, H., Katayama, T., Fukushima, A., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-51298-3 · Cited by 49 · see citing works
Is there a room for GABA in ROS and RNS signalling?
Bor, M., & Türkan, İ. (2019) · Environmental and Experimental Botany · doi:10.1016/j.envexpbot.2019.02.015 · Cited by 48 · see citing works
Oldford, C., Kuksal, N., Gill, R., Young, A., & Mailloux, R. J. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.02.012 · Cited by 46 · see citing works
Can, K., Menzfeld, C., Rinne, L., Rehling, P., Kügler, S., Golubiani, G., Dudek, J., & Müller, M. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00479 · Cited by 46 · see citing works
Comparison of cytotoxicity of IQOS aerosols to smoke from Marlboro Red and 3R4F reference cigarettes
Davis, B. A., To, V., & Talbot, P. (2019) · Toxicology in Vitro · doi:10.1016/j.tiv.2019.104652 · Cited by 44 · see citing works
Tardu, M., Bulut, S., & Kavaklı, İ. H. (2017) · Scientific Reports · doi:10.1038/srep40817 · Cited by 43 · see citing works
Mitochondrial dysfunction in fibroblasts of Multiple System Atrophy
Compagnoni, G. M., Kleiner, G., Bordoni, A., Fortunato, F., Ronchi, D., Salani, S., Guida, M., Corti, C., Pichler, I., Bergamini, C., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.09.018 · Cited by 41 · see citing works
Lu, Z., & Imlay, J. A. (2017) · mBio · doi:10.1128/mbio.01873-16 · Cited by 40 · see citing works
Tang, Y., Wu, J., Sun, X., Tan, S., Li, W., Yin, S., Liu, L., Chen, Y., Liu, Y., Tan, Q., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114237 · Cited by 39 · see citing works
Lindsay, D. P., Camara, A. K. S., Stowe, D. F., Lubbe, R., & Aldakkak, M. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00058 · Cited by 38 · see citing works
Belosludtsev, K. N., Belosludtseva, N. V., Kosareva, E. A., Talanov, E. Y., Gudkov, S. V., & Dubinin, M. V. (2020) · Biochimie · doi:10.1016/j.biochi.2020.07.011 · Cited by 37 · see citing works
Manganese ions induce H2O2 generation at the ubiquinone binding site of mitochondrial complex II
Bonke, E., Zwicker, K., & Dröse, S. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.06.011 · Cited by 39 · see citing works
Self-citationMitoproteomics: Tackling Mitochondrial Dysfunction in Human Disease
Gómez‐Serrano, M., Camafeita, E., Loureiro, M., & Peral, B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1435934 · Cited by 36 · see citing works
Colmenero, F. (2020) · Materials Advances · doi:10.1039/d0ma00019a · Cited by 36 · see citing works
Alqarni, A. M., Niwasabutra, K., Sahlan, M., Fearnley, H., Fearnley, J., Ferro, V. A., & Watson, D. G. (2019) · Metabolites · doi:10.3390/metabo9040075 · Cited by 35 · see citing works
Tomar, N., Zhang, X., Kandel, S. M., Sadri, S., Yang, C., Liang, M., Audi, S. H., Cowley, A. W., & Dash, R. K. (2021) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2021.148518 · Cited by 33 · see citing works
Wang, M., Li, G., Yang, Z., Wang, L., Zhang, L., Wang, T., Zhang, Y., Zhang, S., Han, Y., & Jia, L. (2016) · Oncotarget · doi:10.18632/oncotarget.14097 · Cited by 34 · see citing works
Effects of copper and temperature on heart mitochondrial hydrogen peroxide production
Isei, M. O., & Kamunde, C. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.12.006 · Cited by 35 · see citing works
Protective effects of chlorogenic acid in 3-nitropropionic acid induced toxicity and genotoxicity
Alarcón-Herrera, N., Flores-Maya, S., Bellido, B., García‐Bores, A. M., Mendoza, E., Ávila-Acevedo, J. G., & Hernández, E. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.04.048 · Cited by 32 · see citing works
Bonke, E., Siebels, I., Zwicker, K., & Dröse, S. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.07.026 · Cited by 30 · see citing works
Self-citationMitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma
Zhunussova, A., Vitol, E. A., Polyak, B., Tuleukhanov, S. T., Brooks, A. D., Sensenig, R., Friedman, G., & Orynbayeva, Z. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156818 · Cited by 30 · see citing works
Todt, C. E., Bailey, D. C., Pressley, A. S., Orfield, S. E., Denney, R. D., Snapp, I. B., Negga, R., Bailey, A. C., Montgomery, K. M., Traynor, W. L., et al. (2016) · NeuroToxicology · doi:10.1016/j.neuro.2016.09.011 · Cited by 31 · see citing works
Why do cells need oxygen? Insights from mitochondrial composition and function
Manoj, K. M., Gideon, D. A., & Jaeken, L. (2021) · Cell Biology International · doi:10.1002/cbin.11746 · Cited by 28 · see citing works
Babu, D., Leclercq, G., Goossens, V., Berghe, T. V., Hamme, E. V., Vandenabeele, P., & Lefebvre, R. A. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.02.019 · Cited by 29 · see citing works
Taufani, I. P., Situmorang, J. H., Febriansah, R., Tasminatun, S., Sunarno, S., Yang, L., Chiang, Y., & Huang, C. (2023) · Human & Experimental Toxicology · doi:10.1177/09603271221149663 · Cited by 28 · see citing works
Rajab, B. S., Kassab, S., Stonall, C. D., Daghistani, H., Gibbons, S. M., Mamas, M. A., Smith, D., Mironov, A., Albalawi, Z., Zhang, Y. H., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-04929-1 · Cited by 27 · see citing works
Molecular Bases of Brain Preconditioning
Deryagin, O., Gavrilova, S. A., Латыпович, Г. Х., Golubeva, A. V., Andrianov, V. V., Гульусовна, Я. Г., Валентинович, Б. С., & Кошелев, В. Б. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00427 · Cited by 27 · see citing works
Manoj, K. M., Bazhin, N. M., Tamagawa, H., Jaeken, L., & Parashar, A. (2022) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2022.2060307 · Cited by 26 · see citing works
Zhang, G., Gao, S., Li, X., Zhang, L., Tan, H., Xu, L., Chen, Y., Geng, Y., Lin, Y., Aertker, B. M., et al. (2015) · Scientific Reports · doi:10.1038/srep09858 · Cited by 26 · see citing works
Detection of hydrogen peroxide production in the isolated rat lung using Amplex red
Audi, S. H., Friedly, N., Dash, R. K., Beyer, A., Clough, A. V., & Jacobs, E. R. (2018) · Free Radical Research · doi:10.1080/10715762.2018.1511051 · Cited by 25 · see citing works
Anderson, R. F., Shinde, S. S., Hille, R., Rothery, R. A., Weiner, J. H., Rajagukguk, S., Maklashina, E., & Cecchini, G. (2014) · Biochemistry · doi:10.1021/bi401630m · Cited by 24 · see citing works
Respiratory complex II in mitochondrial dysfunction-mediated cytotoxicity: Insight from cadmium
Belyaeva, E. A. (2018) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2018.06.009 · Cited by 24 · see citing works
DNA‐PKcs and ATM modulate mitochondrial ADP‐ATP exchange as an oxidative stress checkpoint mechanism
Chen, W., Chiang, J., Shang, Z., Palchik, G. A., Newman, C., Zhang, Y., Davis, A. J., Lee, H., & Chen, B. P. C. (2023) · The EMBO Journal · doi:10.15252/embj.2022112094 · Cited by 22 · see citing works
Bianco, M., Lopes, J. A., Beiral, H. J. V., Filho, J. D. D., Frankenfeld, S. P., Fortunato, R. S., Gattass, C. R., Vieyra, A. R., & Takiya, C. M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0218986 · Cited by 22 · see citing works
Preventing Tumour Recurrence after Liver Transplantation: The Role of Machine Perfusion
BOTEON, Y. L., Carvalho, M. F., Panconesi, R., Muiesan, P., & Schlegel, A. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165791 · Cited by 22 · see citing works
Mitochondrial function is impaired in the primary visual cortex in an experimental glaucoma model
Arana, A. G. H., Vitar, R. M. L., Reides, C. G., Calabró, V., Marchini, T., Lerner, S. F., Evelson, P., & Ferreira, S. M. (2021) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2021.108815 · Cited by 21 · see citing works
Trombetti, S., Sessa, R., Catapano, R., Rinaldi, L., Bianco, A. L., Feliciello, A., Izzo, P., & Grosso, M. (2021) · Antioxidants · doi:10.3390/antiox10101603 · Cited by 21 · see citing works
Roma, A., Tcheng, M., Ahmed, N., Walker, S., Jayanth, P., Minden, M. D., Hope, K. J., Rao, P. P. N., Luc, J., Doxey, A. C., et al. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-21-1032 · Cited by 21 · see citing works
Carvalho, M. F., BOTEON, Y. L., Guarrera, J. V., Modi, P. R., Lladó, L., Lurje, G., Kasahara, M., Dutkowski, P., & Schlegel, A. A. (2023) · Hepatology · doi:10.1097/hep.0000000000000394 · Cited by 21 · see citing works
Panconesi, R., Carvalho, M. F., Dondossola, D. E., Muiesan, P., Dutkowski, P., & Schlegel, A. A. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.855263 · Cited by 20 · see citing works
Fan, T. W. ‐., Daneshmandi, S., Cassel, T., Uddin, M. B., Sledziona, J., Thompson, P. T., Lin, P., Higashi, R. M., & Lane, A. N. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200178 · Cited by 20 · see citing works
- Authors
- Dröse, S.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Dröse, Stefan
- ORCID
- Dröse, Stefan
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 1827
- Issue
- 5
- Pages
- 578-587
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2084933852
- Cited by
- 201
- References
- 158
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 14 · 2023: 16 · 2022: 23 · 2021: 19 · 2020: 21 · 2019: 13 · 2018: 23 · 2017: 14 · 2016: 14 · 2015: 14 · 2014: 12 · 2013: 3
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB815)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Keywords
- succinate dehydrogenase, succinate-ubiquinone oxidoreductase, mitochondrial reactive oxygen species, cardioprotection, preconditioning, postconditioning, ischemia-reperfusion injury, respiratory burst, TCA cycle, oxaloacetate, electron transport chain, cardiomyocytes
- MeSH terms
- Electron Transport, Humans, Mitochondria, Models, Biological, Succinates, Myocardial Reperfusion Injury, Reactive Oxygen Species, Ischemic Preconditioning, Myocardial, Electron Transport Complex II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-30.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-30.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
