A common mechanism links differently acting complex II inhibitors to cardioprotection: modulation of mitochondrial reactive oxygen species production
Abstract
In this study, we have analyzed the effect of different cardioprotective complex II inhibitors on the mitochondrial production of reactive oxygen species (ROS) because ROS seem to be essential for signaling during preconditioning to prevent ischemia/reperfusion injury. Despite different binding sites and concentrations required for half-maximal inhibition-ranging from nanomolar for the Q site inhibitor atpenin A5 to millimolar for the succinate analog malonate-all inhibitors modulated ROS production in the same ambivalent fashion: they promoted the generation of superoxide at the Q(o) site of complex III under conditions of "oxidant-induced reduction" but attenuated ROS generated at complex I due to reverse electron transfer. All inhibitors showed these ambivalent effects independent of the presence of K(+). These findings suggest a direct modulation of mitochondrial ROS generation during cardioprotection via complex II inhibition and question the recently proposed role of complex II as a regulatory component of the putative mitochondrial K(ATP) channel.
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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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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).”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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'.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
An 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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [16]
Cites
Topology of superoxide production from different sites in the mitochondrial electron transport chain
St-Pierre, J., Buckingham, J. A., Roebuck, S. J., & Brand, M. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207217200 · Cited by 1,545 · 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
Complex iii releases superoxide to both sides of the inner mitochondrial membrane
Muller, F. L., Liu, Y., & Van Remmen, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407715200 · Cited by 1,036 · 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
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
Kußmaul, L., & Hirst, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510977103 · Cited by 720 · 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
Lambert, A. J., & Brand, M. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406576200 · Cited by 480 · 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-citationFunctional Modules and Structural Basis of Conformational Coupling in Mitochondrial Complex I
Hunte, C., Zickermann, V., & Brandt, U. (2010) · Science · doi:10.1126/science.1191046 · Cited by 370 · see citing works
Self-citationThe 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
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
Self-citationHorsefield, 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
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
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
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
Muller, F., Crofts, A. R., & Kramer, D. M. (2002) · Biochemistry · doi:10.1021/bi025581e · Cited by 163 · see citing works
Galkin, A. S., & Brandt, U. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504709200 · Cited by 162 · see citing works
Self-citationCardioprotection 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
Facundo, H. T., de Paula, J. G., & Kowaltowski, A. J. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.001 · Cited by 123 · 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
Dröse, S., Brandt, U., & Hanley, P. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602570200 · Cited by 105 · see citing works
Self-citationMitochondrial 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
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
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-citationDröse, 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-citationSarewicz, M., Borek, A., Cieluch, E., Świerczek, M., & Osyczka, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.07.005 · Cited by 63 · see citing works
Borek, A., Sarewicz, M., & Osyczka, A. (2008) · Biochemistry · doi:10.1021/bi801207f · Cited by 62 · 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
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
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
Adebiyi, A., McNally, E. M., & Jaggar, J. H. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.048165 · Cited by 42 · see citing works
Inhibition of mitochondrial metabolism by the diabetogenic thiadiazine diazoxide—II
Portenhauser, R., Schäfer, G., & Trolp, R. (1971) · Biochemical Pharmacology · doi:10.1016/0006-2952(71)90171-7 · Cited by 32 · 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
Substrate Redox Potential Controls Superoxide Production Kinetics in the Cytochrome bc Complex
Cape, J. L., Aidasani, D., Kramer, D., & Bowman, M. K. (2009) · Biochemistry · doi:10.1021/bi901205w · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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-citationMitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies
Lesnefsky, E. J., Chen, Q., Tandler, B., & Hoppel, C. L. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103335 · Cited by 443 · see citing works
Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies
Soares, R. O. D. S., Losada, D. M., Jordani, M. C., Évora, P. R. B., & Castro-e-Silva, O. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205034 · Cited by 415 · 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-citationCadmium-Induced Oxidative Stress: Focus on the Central Nervous System
Branca, J. J. V., Fiorillo, C., Carrino, D., Paternostro, F., Taddei, N., Gulisano, M., Pacini, A., & Becatti, M. (2020) · Antioxidants · doi:10.3390/antiox9060492 · Cited by 319 · see citing works
Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.01.004 · Cited by 201 · see citing works
Self-citationKamiński, M. M., Sauer, S. W., Kamiński, M., Opp, S., Ruppert, T., Grigaravičius, P., Grudnik, P., Gröne, H., Krammer, P. H., & Gülow, K. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.10.009 · Cited by 200 · 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-citationMitochondrial 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
Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?
Xu, Y., Xue, D., Bankhead, A., & Neamati, N. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01013 · Cited by 161 · see citing works
Messeder, D. J., Caverzan, A., Rauber, R., Ferreira, E. D. S., Margis-Pinheiro, M. M. A. N., & Galina, A. (2015) · New Phytologist · doi:10.1111/nph.13515 · Cited by 158 · 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-citationValls-Lacalle, L., Barba, I., Miró‐Casas, E., Alburquerque-Béjar, J. J., Ruiz‐Meana, M., Fuertes‐Agudo, M., Rodríguez‐Sinovas, A., & David Garcia-dorado, A. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv279 · Cited by 149 · 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
Siebels, 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-citationMitochondrial 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
Multiplicity of effectors of the cardioprotective agent, diazoxide
Coetzee, W. A. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.06.007 · Cited by 92 · see citing works
Valls-Lacalle, L., Barba, I., Miró-Casas, E., Ruiz-Meana, M., Rodríguez-Sinovas, A., & García-Dorado, D. (2018) · Scientific Reports · doi:10.1038/s41598-018-20866-4 · Cited by 88 · see citing works
Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel
Wojtovich, A. P., Smith, C. O., Haynes, C. M., Nehrke, K. W., & Brookes, P. S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.12.007 · Cited by 83 · see citing works
Kamiński, M. M., Röth, D., Krammer, P. H., & Gülow, K. (2013) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-013-0235-0 · Cited by 72 · see citing works
Mitochondrial Potassium Channels as Druggable Targets
Wrzosek, A., Augustynek, B., Żochowska, M., & Szewczyk, A. M. (2020) · Biomolecules · doi:10.3390/biom10081200 · Cited by 72 · see citing works
Succinate dehydrogenase: Prospect for neurodegenerative diseases
Farshbaf, M. J., & Kiani‐Esfahani, A. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.12.002 · Cited by 69 · 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
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
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
Kôrge, P., Calmettes, G., & Weiss, J. N. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.002 · Cited by 59 · see citing works
Mitochondrial metabolism: a common link between neuroinflammation and neurodegeneration
Garabadu, D., Agrawal, N., Sharma, A., & Sharma, S. (2019) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000505 · Cited by 57 · see citing works
Hofmann, J. D., Otarashvili, G., Mészáros, A., Ebner, S., Weißenbacher, A., Cardini, B., Oberhuber, R., Resch, T., Öfner, D., Schneeberger, S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093132 · Cited by 59 · 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
Shin, J. S., So, W. M., Kim, S. Y., Noh, M., Hyoung, S., Yoo, K. S., & Shin, J. S. (2020) · Plant Science · doi:10.1016/j.plantsci.2020.110458 · Cited by 46 · see citing works
Soares, M. V., Mesadri, J., Gonçalves, D. F., Cordeiro, L. M., da Silva, A. F., Baptista, F. B. O., Wagner, R. C., Corte, C. L. D., Soares, F. A. A., & Ávila, D. S. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.118856 · Cited by 44 · see citing works
Agarwal, B., Dash, R. K., Stowe, D. F., Bosnjak, Z. J., & Camara, A. K. S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.11.006 · Cited by 41 · see citing works
Jespersen, N. R., Hjortbak, M. V., Lassen, T. R., Støttrup, N. B., Johnsen, J., Tonnesen, P. T., Larsen, S., Kimose, H., & Bøtker, H. E. (2020) · Scientific Reports · doi:10.1038/s41598-020-67247-4 · Cited by 40 · see citing works
Powerhouse down: Complex II dissociation in the respiratory chain
Hwang, M., Rohlena, J., Dong, L., Neužil, J., & Grimm, S. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.06.001 · Cited by 39 · see citing works
Manente, A. G., Valenti, D., Pinton, G., Jithesh, P. V., Daga, A., Rossi, L., Gray, S. G., O'Byrne, K. J., Fennell, D. A., Vacca, R. A., et al. (2013) · Oncogenesis · doi:10.1038/oncsis.2013.32 · Cited by 40 · see citing works
Wang, Y.-H., Li, S.-A., Huang, C.-H., Su, H.-H., Chen, Y., Chang, J. T., & Huang, S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00636 · Cited by 37 · see citing works
The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection
Smith, C. O., Nehrke, K. W., & Brookes, P. S. (2017) · Biochemical Journal · doi:10.1042/bcj20160623 · 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-citationBarnett, D., Zimmer, T. S., Booraem, C., Palaguachi, F., Meadows, S. M., Xiao, H., Wong, M. Y., Luo, W., Gan, L., Chouchani, E. T., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01390-y · Cited by 39 · see citing works
Cellular crosstalk in cardioprotection: Where and when do reactive oxygen species play a role?
Martins‐Marques, T., Rodríguez‐Sinovas, A., & Girão, H. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.03.044 · Cited by 38 · see citing works
Koenitzer, J. R., Bonacci, G., Woodcock, S. R., Chen, C.-S., Cantú‐Medellín, N., Kelley, E. E., & Schopfer, F. J. (2015) · Redox Biology · doi:10.1016/j.redox.2015.11.002 · Cited by 35 · see citing works
Dong, L., & Neužil, J. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-394625-6.00008-8 · Cited by 33 · see citing works
Kôrge, P., Calmettes, G., John, S., & Weiss, J. N. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.768317 · Cited by 32 · see citing works
Krautwald, S., Nilewski, C., Mori, M., Shiomi, K., Ōmura, S., & Carreira, E. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201511672 · Cited by 28 · see citing works
Controlled power: how biology manages succinate-driven energy release
Mookerjee, S. A., Gerencser, A. A., Watson, M. A., & Brand, M. D. (2021) · Biochemical Society Transactions · doi:10.1042/bst20211032 · Cited by 21 · see citing works
Du, J., Yu, S., Wang, D., Chen, S., Chen, S., Zheng, Y., Wang, N., Chen, S., Li, J., & Shen, B. (2020) · Rheumatology · doi:10.1093/rheumatology/keaa063 · Cited by 17 · see citing works
Sadri, S., Tomar, N., Yang, C., Audi, S. H., Cowley, A. W., & Dash, R. K. (2023) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2023.109690 · Cited by 17 · see citing works
Traditional and novel tools to probe the mitochondrial metabolism in health and disease
Zhang, Y., & Avalos, J. L. (2017) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1373 · Cited by 17 · see citing works
Sha, D., Wang, L., Zhang, J., Qian, L., Li, Q., Li, J., Qian, J., Gu, S., Han, L., Xu, P., et al. (2014) · Brain Research · doi:10.1016/j.brainres.2014.07.043 · Cited by 15 · see citing works
Repeated Exposure to Hyperbaric Hyperoxia Affects Mitochondrial Functions of the Lung Fibroblasts
Dejmek, J., Kohoutová, M., Kripnerová, M., Čedíková, M., Tůma, Z., Babuška, V., Bolek, L., & Kuncová, J. (2018) · Physiological Research · doi:10.33549/physiolres.934046 · Cited by 14 · see citing works
Sánchez‐Duarte, E., Cortés‐Rojo, C., Sánchez‐Briones, L. A., Campos‐García, J., Saavedra‐Molina, A., Delgado‐Enciso, I., López-Lemus, U. A., & Montoya-Pérez, R. D. C. (2020) · The Journal of Membrane Biology · doi:10.1007/s00232-020-00129-y · Cited by 13 · see citing works
Sun, L., Zhou, F., Shao, Y., Lv, Z., & Li, C. (2020) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2020.04.060 · Cited by 12 · see citing works
Gori, D. N. P., Ruatta, S., Fló, M., Alberca, L. N., Bellera, C. L., Park, S., Heo, J., Lee, H., Park, K.-H. P., Pritsch, O., et al. (2023) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2022.1082065 · Cited by 9 · see citing works
Krautwald, S., Nilewski, C., Mori, M., Shiomi, K., Ōmura, S., & Carreira, E. M. (2016) · Angewandte Chemie · doi:10.1002/ange.201511672 · Cited by 7 · see citing works
Involvement of connexin 43 in myocardial ischemia–reperfusion injury
Ruiz‐Meana, M., Inserte, J., Consegal, M., & Rodríguez‐Sinovas, A. (2025) · Cell and Tissue Research · doi:10.1007/s00441-025-03987-x · Cited by 6 · see citing works
Effect of Melatonin and Salicylic Acid on ROS Generation by Mitochondria of Lupine Seedlings
Андреевич, Б. П., Шугаева, Н. А., & Григорьевич, Ш. А. (2021) · Russian Journal of Plant Physiology · doi:10.1134/s1021443721040038 · Cited by 6 · see citing works
Ткаченко, Г. М., Grudniewska, J., & Kurhaluk, N. (2022) · Fisheries & Aquatic Life · doi:10.2478/aopf-2022-0014 · Cited by 5 · see citing works
The nuanced role of mitochondrial ROS in modulating aging and aging hallmarks
Müller-Eigner, A., Morin, E., Morton, K. S., & Wojtovich, A. P. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104319 · Cited by 2 · see citing works
Zhao, Y., Xu, Z., Bian, C., Huang, L., Xu, T., Chen, M., Sun, T., Deng, X., 余秀君, Song, L., et al. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115180 · Cited by 1 · see citing works
Mufaiduddin, M., Innelya, I., & Rahmatika, A. (2024) · SCRIPTA SCORE Scientific Medical Journal · doi:10.32734/scripta.v5i2.15156
Role of SDH in Cardiovascular Disorders
Patil, V. M., Masand, N., Krishnamurthy, P. T., & Gupta, S. P. (2025) · Springer eBooks · doi:10.1007/978-981-96-6831-1_6
Understanding Oxidative Stress in Ischemia-Reperfusion Injury
Singh, A., Gupta, S., Das, S., Gupta, S., Chaudhary, R., & Mishra, V. (2026) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-032-19837-2_9
Electrophilic Nitro-Fatty Acid Regulation of Mitochondrial Function
Koenitzer, J. R. (2012) · D-Scholarship@Pitt (University of Pittsburgh)
- Authors
- Dröse, S., Bleier, L., & Brandt, U.
- Affiliations
- Goethe University Frankfurt (DE)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 79
- Issue
- 5
- Pages
- 814-822
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2115556604
- Cited by
- 64
- References
- 40
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 10 · 2019: 2 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 7 · 2012: 5
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cell death mechanisms and regulation
- Keywords
- complex II inhibition, cardioprotection, mitochondrial reactive oxygen species, superoxide, malonate, ischemia-reperfusion injury, preconditioning, reverse electron transfer, mitochondrial complex I, mitochondrial KATP channels, mitochondrial electron transport chain
- MeSH terms
- Animals, Binding Sites, Cardiotonic Agents, Cattle, Enzyme Inhibitors, Mitochondria, Heart, Models, Molecular, Pyridones, Submitochondrial Particles, Thenoyltrifluoroacetone, Reactive Oxygen Species, Electron Transport Complex II, Rats
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