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Mechanism of Superoxide and Hydrogen Peroxide Formation by Fumarate Reductase, Succinate Dehydrogenase, and Aspartate Oxidase
Open accessAbstract
Oxidative stress is created in aerobic organisms when molecular oxygen chemically oxidizes redox enzymes, forming superoxide (O2*-) and hydrogen peroxide (H2O2). Prior work identified several flavoenzymes from Escherichia coli that tend to autoxidize. Of these, fumarate reductase (Frd) is notable both for its high turnover number and for its production of substantial O2*- in addition to H2O2. We have sought to identify characteristics of Frd that predispose it to this behavior. The ability of excess succinate to block autoxidation and the inhibitory effect of lowering the flavin potential indicate that all detectable autoxidation occurs from its FAD site, rather than from iron-sulfur clusters or bound quinones. The flavin adenine dinucleotide (FAD) moiety of Frd is unusually solvent-exposed, as evidenced by its ability to bind sulfite, and this may make it more likely to react adventitiously with O2*-. The autoxidizing species is apparently fully reduced flavin rather than flavosemiquinone, since treatments that more fully reduce the enzyme do not slow its turnover number. They do, however, switch the major product from O2*- to H2O2. A similar effect is achieved by lowering the potential of the proximal [2Fe-2S] cluster. These data suggest that Frd releases O2*- into bulk solution if this cluster is available to sequester the semiquinone electron; otherwise, that electron is rapidly transferred to the nascent superoxide, and H2O2 is the product that leaves the active site. This model is supported by the behavior of "aspartate oxidase" (aspartate:fumarate oxidoreductase), an Frd homologue that lacks Fe-S clusters. Its dihydroflavin also reacts avidly with oxygen, and H2O2 is the predominant product. In contrast, succinate dehydrogenase, with high potential clusters, generates O2*- exclusively. The identities of enzyme autoxidation products are significant because O2*- and H2O2 damage cells in different ways.
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“Both enzymes produced ROS with a linear dependence on the dissolved oxygen concentration, although SQR produced ROS at a much lower rate.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [101]
In the citing paper
“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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [101]
In the citing paper
“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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [101]
In the citing paper
“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].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [101]
In the citing paper
“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).”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [101]
In the citing paper
“An impairment in the normal removal of electrons from the flavin group in SdhA could promote superoxide generation through the autoxidation of the reduced flavin group by O 2 in the matrix (34, 38, 46, 51).”
From Loss of the SdhB, but Not the SdhA, Subunit of Complex II Triggers Reactive Oxygen Species-Dependent Hypoxia-Inducible Factor Activation and Tumorigenesis (2008) · cites this paper as [34]
In the citing paper
“Some evidence suggests that the flavin adenine dinucleotide site in SdhA is the principal source of superoxide generation, due to the exposure of that moiety to the aqueous environment and the high electron density that develops when the electron flux downstream from that site is obstructed (34, 51).”
From Loss of the SdhB, but Not the SdhA, Subunit of Complex II Triggers Reactive Oxygen Species-Dependent Hypoxia-Inducible Factor Activation and Tumorigenesis (2008) · cites this paper as [34]
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Citations
Cites
Experiments in molecular genetics
Miller, J. H. (1972) · Medical Entomology and Zoology · Cited by 27,157
McCord, J. M., & Fridovich, I. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63504-5 · Cited by 12,952
Zhou, M., Diwu, Z. J., Panchuk-Voloshina, N., & Haugland, R. P. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2391 · Cited by 1,400
Storz, G., & Imlayt, J. A. (1999) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(99)80033-2 · Cited by 1,077
Quantitative Aspects of the Production of Superoxide Anion Radical by Milk Xanthine Oxidase
Fridovich, I. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62884-4 · Cited by 1,035
An Enzyme-Based Theory of Obligate Anaerobiosis: The Physiological Function of Superoxide Dismutase
McCord, J. M., Keele, B. B., & Fridovich, I. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.5.1024 · Cited by 976
Superoxide accelerates DNA damage by elevating free-iron levels
Keyer, K., & Imlay, J. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13635 · Cited by 841
Self-citationActivation of molecular oxygen by flavins and flavoproteins.
Massey, V. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31664-2 · Cited by 823
Seaver, L. C., & Imlay, J. A. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.24.7173-7181.2001 · Cited by 797
Self-citationCarlioz, A., & Touati, D. (1986) · The EMBO Journal · doi:10.1002/j.1460-2075.1986.tb04256.x · Cited by 784
Flagged first, then by citations
Research works printed but not linked: 2
- Ackrell, 1992, 3, 229
- Guest, 1981, J. Gen. Microbiol., 122, 171
Cited by
Sorted by citations
Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014) · Physiological Reviews · doi:10.1152/physrev.00026.2013 · Cited by 5,383
“Some studies point to flavins (flavin adenine nucleotides, FAD) of SDH rather than other electron-carrying components (such as iron-sulfur clusters or quinones) as the site of autoxidation responsible for generating ROS (200, 293, 294).”
BackgroundImlay, J. A. (2003) · Annual Review of Microbiology · doi:10.1146/annurev.micro.57.030502.090938 · Cited by 2,201
Self-citationImlay, J. A. (2013) · Nature Reviews Microbiology · doi:10.1038/nrmicro3032 · Cited by 1,749
Self-citationWater-Splitting Chemistry of Photosystem II
McEvoy, J. P., & Brudvig, G. W. (2006) · Chemical Reviews · doi:10.1021/cr0204294 · Cited by 1,542
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
“The rates during succinate oxidation by fumarate reductase, which catalyses the reverse reaction in Escherichia coli and lacks this mechanism, are much greater (Messner and Imlay, 2002).”
BackgroundMitochondrial ROS-induced ROS release: An update and review
Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2006) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2006.04.029 · Cited by 1,099
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063
Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins
Brand, M. D., Affourtit, C., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Pakay, J. L., & Parker, N. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.05.034 · Cited by 1,032
Hydrogen peroxide metabolism and functions in plants
Smirnoff, N., & Arnaud, D. (2018) · New Phytologist · doi:10.1111/nph.15488 · Cited by 991
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
Yamanaka, M., Hara, K., & Kudo, J. (2005) · Applied and Environmental Microbiology · doi:10.1128/aem.71.11.7589-7593.2005 · Cited by 907
“Previous in vitro analyses of the E. coli respiratory chain indicated that reactive oxygen species are generated primarily by the autoxidation of reduced dehydrogenases, such that NADH dehydrogenase II reacted with oxygen at a substantial rate, succinate dehydrogenase produced scant but still detectable reactive oxyge…”
BackgroundCrystal 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
Kußmaul, L., & Hirst, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510977103 · Cited by 745
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
“A comparison of enzymes with autoxidizable flavins (xanthine oxidase, aspartate oxidase, and fumarate reductase) suggested that the presence and potential of a nearby electron accepting [Fe-S] species determined whether flavin oxidation was monovalent or divalent (24).”
BackgroundMitochondrial tumour suppressors: a genetic and biochemical update
Gottlieb, E., & Tomlinson, I. P. M. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1737 · Cited by 626
Cardiac Mitochondria and Reactive Oxygen Species Generation
Chen, Y., & Zweier, J. L. (2014) · Circulation Research · doi:10.1161/circresaha.114.300559 · Cited by 618
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
High Levels of Intracellular Cysteine Promote Oxidative DNA Damage by Driving the Fenton Reaction
Park, S., & Imlay, J. A. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.6.1942-1950.2003 · Cited by 485
“H2O2 is formed in bacteria when molecular oxygen oxidizes redox enzymes (32, 33).”
BackgroundSelf-citationPotentiating antibacterial activity by predictably enhancing endogenous microbial ROS production
Brynildsen, M. P., Winkler, J. A., Spina, C. S., MacDonald, I. C., & Collins, J. J. (2013) · Nature Biotechnology · doi:10.1038/nbt.2458 · Cited by 466
Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli
Dwyer, D. J., Kohanski, M. A., Hayete, B., & Collins, J. J. (2007) · Molecular Systems Biology · doi:10.1038/msb4100135 · Cited by 470
“S clusters (SdhB subunit) and has been shown to result in the generation of superoxide (Messner and Imlay, 2002); accordingly, we chose to study the effect of norfloxacin on the growth of D sdhB cells in order to reduce both the level of endogenous Fe–”
InfluentialGordon, O., Slenters, T. V., Brunetto, P. S., Villaruz, A. E., Sturdevant, D. E., Otto, M. J., Landmann, R. M., & Fromm, K. M. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01830-09 · Cited by 445
“A possible source of ROS might be electrons trapped in the respiratory chain (30, 31), as suggested by the gene upregulation of the terminal and downregulation of the initial respiratory enzymes.”
BackgroundGuzy, R. D., Sharma, B., Bell, E., Chandel, N. S., & Schumacker, P. T. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01338-07 · Cited by 427
“tion of the reduced flavin group by O2 in the matrix (34, 38, 46, 51).”
BackgroundWhy do bacteria use so many enzymes to scavenge hydrogen peroxide?
Mishra, S., & Imlay, J. A. (2012) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2012.04.014 · Cited by 433
Self-citationReactive Oxygen Species Production by Mitochondria
Lambert, A. J., & Brand, M. D. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-521-3_11 · Cited by 385
MacKenzie, E. D., Selak, M. A., Tennant, D. A., Payne, L. J., Crosby, S., Frederiksen, C. M., Watson, D. G., & Gottlieb, E. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01927-06 · Cited by 359
“The first suggested that reactive oxygen species (ROS) from an impaired complex II of the electron transport chain (18, 30) potentially inhibit PHDs (7).”
BackgroundHow oxygen attacks [FeFe] hydrogenases from photosynthetic organisms
Stripp, S. T., Goldet, G., Brandmayr, C., Sanganas, O., Vincent, K. A., Haumann, M., Armstrong, F. A., & Happe, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905343106 · Cited by 361
Cadmium-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 327
Pumirat, P., Boonyuen, U., Vanaporn, M., Pinweha, P., Tandhavanant, S., Korbsrisate, S., & Chantratita, N. (2014) · BMC Microbiology · doi:10.1186/1471-2180-14-1 · Cited by 287
“Several reports have indicated that bacterial dehydrogenases are important enzymes in oxidative stress response, such as NADH dehydrogenase, lactate dehydrogenase, formate dehydrogenase, succinate dehydrogenase, fumarate reductase, and glutathione-dependent formaldehyde dehydrogenase [27-32].”
BackgroundAitken, R. J., Whiting, S., Iuliis, G. N. D., McClymont, S., Mitchell, L. A., & Baker, M. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.366690 · Cited by 266
“Rather, the primary impact of 4HNE is to covalently bind SDHA disrupting the functionality of this molecule so that it auto-oxidizes and adventitiously transfers electrons to oxygen in the manner described by Messner and Imlay (35).”
BackgroundBiochemical dysfunction in heart mitochondria exposed to ischaemia and reperfusion
Solaini, G., & Harris, D. A. (2005) · Biochemical Journal · doi:10.1042/bj20042006 · Cited by 255
Hermes‐Lima, M., Moreira, D. C., Rivera‐Ingraham, G. A., Giraud‐Billoud, M., Genaro‐Mattos, T. C., & Campos, E. G. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.07.156 · Cited by 246
“This would not only cause succinate to accumulate but additionally will cause ROS generation because fumarate reductase has been demonstrated to be a powerful O2•− generator (e.g., Imlay, 1995; Messner and Imlay, 2002; Turrens, 1987).”
Mitochondrial Complex II in the Post-ischemic Heart
Chen, Y., Chen, C., Pfeiffer, D. R., & Zweier, J. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702294200 · Cited by 230
How radiation kills cells: Survival of and under oxidative stress
Ghosal, D., Omelchenko, M. V., Gaidamakova, E. K., Matrosova, V. Y., Vasilenko, A., Venkateswaran, A., Zhai, M., Kostandarithes, H. M., Brim, H., & Makarova, K. S. (2005) · FEMS Microbiology Reviews · doi:10.1016/j.femsre.2004.12.007 · Cited by 225
“Since bound Fe(II), particularly from iron–sulfur (2Fe–2S, 4Fe–4S) clusters [5,56], can be released within cells when they have been oxidatively damaged [57], HO generated by radiolysis might increase the amount of ‘‘free Fe(II)’’ in cells, with the result that irradiated cells transferred to recovery medium become su…”
BackgroundInfluentialAre Respiratory Enzymes the Primary Sources of Intracellular Hydrogen Peroxide?
Seaver, L. C., & Imlay, J. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408754200 · Cited by 231
Self-citationAndrés, C. M. C., Pérez de la Lastra, J. M., Juan, C. A., Plou, F. J., & Pérez-Lebeña, E. (2022) · Stresses · doi:10.3390/stresses2030019 · Cited by 218
“Hydrogen peroxide is formed as a product of the monovalent reduction of superoxide or by the divalent reduction of oxygen [12].”
BackgroundMitochondria and Reactive Oxygen Species. Which Role in Physiology and Pathology?
Lenaz, G. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_5 · Cited by 219
Plotnikov, E. Y., Kazachenko, A. V., Vyssokikh, M. Y., Vasileva, A. K., Tcvirkun, D. V., Исаев, Н. К., Kirpatovsky, V. I., & Zorov, D. B. (2007) · Kidney International · doi:10.1038/sj.ki.5002568 · Cited by 211
The disulfide relay system of mitochondria is connected to the respiratory chain
Bihlmaier, K., Mesecke, N., Terziyska, N., Bien, M., Hell, K., & Herrmann, J. M. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200707123 · Cited by 210
“The mitochondrial IMS is anyway highly at risk of the ROS production by respiratory chain complexes (Guo and Lemire, 2003; Kussmaul and Hirst, 2006; Messner and Imlay, 2002; Sun and Trumpower, 2003; Yankovskaya et al., 2003).”
BackgroundDröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.01.004 · Cited by 201
The respiratory chain of Corynebacterium glutamicum
Bott, M., & Niebisch, A. (2003) · Journal of Biotechnology · doi:10.1016/s0168-1656(03)00144-5 · Cited by 197
Redout, E. M., WAGNER, M., Zuidwijk, M. J., Boer, C., Musters, R. J. P., VANHARDEVELD, C., Paulus, W. J., & Simonides, W. S. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.05.012 · Cited by 188
“Although our in vitro data and the studies cited above indicate Complex III as the main site of ROS release, other studies of Complex II in mitochondria from yeast and various tissues suggest that this complex is also a potential site of ROS production [16,47–49].”
BackgroundAstrom, K., Cohen, J. E., Willett-Brozick, J. E., Aston, C. E., & Baysal, B. E. (2003) · Human Genetics · doi:10.1007/s00439-003-0969-6 · Cited by 187
“) to ubiquinol (QH2) by means of the electrons (e–) derived from the oxidation of succinate to fumarate in the Krebs cycle, and/or the complete transfer of the electrons through MTCII prevents their accumulation in the flavoprotein and iron-sulfur subunits, which might lead to ROS production through chemical interacti…”
BackgroundThe assembly of succinate dehydrogenase: a key enzyme in bioenergetics
Moosavi, B., Berry, E. A., Zhu, X., Yang, W., & Yang, G. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03200-7 · Cited by 184
Two sources of endogenous hydrogen peroxide in Escherichia coli
Korshunov, S., & Imlay, J. A. (2010) · Molecular Microbiology · doi:10.1111/j.1365-2958.2010.07059.x · Cited by 184
“…to the form that we now know as succinate dehydrogenase: the elevation of its iron-sulphur cluster potentials and the addition of an accessory haem pull electron density away from the flavin and thereby strongly suppresses its oxidation rate (Messner and Imlay, 2002; Yandovskaya et al., 2003).”
BackgroundMethodInfluentialSelf-citationDetection and Quantification of Superoxide Formed within the Periplasm of Escherichia coli
Korshunov, S., & Imlay, J. A. (2006) · Journal of Bacteriology · doi:10.1128/jb.00554-06 · Cited by 182
“22 V) is the direct electron donor (31).”
BackgroundSelf-citationBurwell, L. S., & Brookes, P. S. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1845 · Cited by 177
“Mitochondria are a major source of reactive oxygen species (ROS), from sites within the ETC (117, 128, 167, 230) and the Krebs cycle (231).”
Fan, T., Sun, G., Sun, X., Zhao, L., Zhong, R., & Peng, Y. (2019) · Cancers · doi:10.3390/cancers11030317 · Cited by 171
“In addition, ROS can be produced by the impairment of SDH/complex II (Figure 5) [91], and 3-BrPA could inhibit this respiratory enzyme.”
BackgroundSantos, A. L., Sinha, S., & Lindner, A. B. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1941285 · Cited by 168
Genome‐scale model for Clostridium acetobutylicum: Part I. Metabolic network resolution and analysis
Senger, R. S., & Papoutsakis, E. T. (2008) · Biotechnology and Bioengineering · doi:10.1002/bit.22010 · Cited by 175
Real-time electron transfer in respiratory complex I
Verkhovskaya, M. L., Belevich, N. P., Euro, L., Wikström, M. K. F., & Verkhovsky, M. I. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711249105 · Cited by 169
“Therefore, our finding is consistent with the proposal that an Fe/S center near the flavin captures the electron from the FMN radical before it can react with nascent superoxide to form hydrogen peroxide (17).”
BackgroundResultMitochondria and cancer: is there a morphological connection?
Alirol, E., & Martinou, J. (2006) · Oncogene · doi:10.1038/sj.onc.1209600 · Cited by 171
“Many scientists in the field of cancer research may have considered mitochondria only as a reservoir for stocking harmful molecules such as ROS and apoptotic proteins.”
BackgroundInfluentialMitochondrial 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 166
“in normal cells) [36,47,55], this is not the case for S.”
BackgroundAlternate metabolism during the dauer stage of the nematode Caenorhabditis elegans
Burnell, A. M., Houthoofd, K., O’Hanlon, K. A., & Vanfleteren, J. R. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.09.006 · Cited by 159
How Microbes Defend Themselves From Incoming Hydrogen Peroxide
Sen, A., & Imlay, J. A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.667343 · Cited by 153
“The small size of O2 prevents its exclusion from most active sites, and its collision with reduced flavins triggers the consecutive transfer of one or two electrons, generating O2 or H2O2, respectively (19).”
BackgroundSelf-citationChoi, H., Yang, Z., & Weisshaar, J. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417703112 · Cited by 147
“5), causing electrons to “pile up” in the respiratory electron transport chain (26).”
BackgroundSeib, K. L., Wu, H., Kidd, S. P., Apicella, M. A., Jennings, M. P., & McEwan, A. G. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00044-05 · Cited by 143
“The major source of endogenous ROS in E. coli is a result of auto-oxidation of components of the aerobic respiratory chain (i.e., NADH dehydrogenase [complex I] and succinate dehydrogenase [complex II], as well as fumarate reductase) (124, 167, 168, 178), leading to the generation of 5 (cid”
Mitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator
Chong, S. J. F., Low, I. C. C., & Pervaiz, S. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.06.002 · Cited by 142
“Aside from the NADH-driven ROS production from complex I and subsequently complex III, complex II has also been demonstrated as a source of ROS production (Gleason et al., 2011; Messner and Imlay, 2002; Quinlan et al., 2012; Zhang et al., 1998).”
Esterházy, D., King, M. S., Yakovlev, G., & Hirst, J. (2008) · Biochemistry · doi:10.1021/bi702243b · Cited by 144
“Similar mechanisms have been proposed previously, for xanthine oxidase, fumarate reductase, and succinate dehydrogenase (47, 48).”
BackgroundHirst, J., & Roessler, M. M. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.12.009 · Cited by 139
Siebels, I., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.06.005 · Cited by 130
Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug
Cardaci, S., Desideri, E., & Ciriolo, M. R. (2012) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-012-9422-7 · Cited by 134
From Mitochondria to Disease: Role of the Renin-Angiotensin System
de Cavanagh, E. M. V., Inserra, F., Ferder, M., & Ferder, L. (2007) · American Journal of Nephrology · doi:10.1159/000107757 · Cited by 124
Protein-mediated assembly of succinate dehydrogenase and its cofactors
Vranken, J. G. V., Na, U., Winge, D. R., & Rutter, J. P. (2014) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2014.990556 · Cited by 122
“This oxidation causes a reduction of the FAD cofactor, which then reduces molecular oxygen to form superoxide (Messner & Imlay, 2002).”
BackgroundHow Microbes Evolved to Tolerate Oxygen
Khademian, M., & Imlay, J. A. (2020) · Trends in Microbiology · doi:10.1016/j.tim.2020.10.001 · Cited by 112
Self-citationSayed, A. A., Cook, S. K., & Williams, D. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512601200 · Cited by 115
SDHAF4 Promotes Mitochondrial Succinate Dehydrogenase Activity and Prevents Neurodegeneration
Vranken, J. G. V., Bricker, D. K., Dephoure, N., Gygi, S. P., Cox, J. E., Thummel, C. S., & Rutter, J. P. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.012 · Cited by 108
“We propose that this unique demand might relate to the need to protect the redoxactive cofactors present in many ETC complex subunits (Messner and Imlay, 2002).”
BackgroundOfoedu, C. E., You, L., Osuji, C. M., Iwouno, J. O., Kabuo, N. O., Ojukwu, M., Agunwah, I. M., Chacha, J. S., Muobike, O. P., Agunbiade, A. O., et al. (2021) · Foods · doi:10.3390/foods10040699 · Cited by 109
The ArcAB Two-Component System: Function in Metabolism, Redox Control, and Infection
Brown, A. N., Anderson, M. T., Bachman, M. A., & Mobley, H. L. T. (2022) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00110-21 · Cited by 109
“The metabolic pathways ArcA controls are large sources of internal ROS production and thus may need to be repressed when the cell faces an exogenous ROS threat (206, 207).”
BackgroundGuo, F., Yang, W., Jiang, W., Geng, S., Peng, T., & Li, J. L. (2012) · Environmental Microbiology · doi:10.1111/j.1462-2920.2012.02707.x · Cited by 108
Adaptation in Bacillus cereus: From Stress to Disease
Duport, C., Jobin, M.-P., & Schmitt, P. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01550 · Cited by 104
“The aerobic respiratory chain is not only a main source of ATP but it also a major source of reactive oxygen species (ROS; Gonzalez-Flecha and Demple, 1995; Messner and Imlay, 2002; Mailloux et al., 2011).”
BackgroundScavenging of superoxide by a membrane-bound superoxide oxidase
Lundgren, C. A. K., Sjöstrand, D., Biner, O., Bennett, M. D., Rudling, A., Johansson, A.-L., Brzezinski, P., Carlsson, J., von Ballmoos, C., & Högbom, M. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0072-x · Cited by 110
Guo, J., & Lemire, B. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306312200 · Cited by 103
Quinlan, C. L., Perevoschikova, I. V., Goncalves, R. L. S., Hey‐Mogensen, M., & Brand, M. D. (2013) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-405883-5.00012-0 · Cited by 101
“The enzyme isolated from Escherichia coli or purified from bovine heart has been reported to generate superoxide under some conditions (Messner & Imlay, 2002; Zhang, Yu, & Yu, 1998).”
Mitochondrial production of reactive oxygen species
Grivennikova, V. G., & Vinogradov, A. D. (2013) · Biochemistry (Moscow) · doi:10.1134/s0006297913130087 · Cited by 102
Yoon, Y.-S., Byun, H.-O., Cho, H., Kim, B.-K., & Yoon, G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308489200 · Cited by 91
Mishra, S., & Imlay, J. A. (2013) · Molecular Microbiology · doi:10.1111/mmi.12438 · Cited by 91
“Strikingly, obligate anaerobes may have high titres of low-potential flavoproteins, such as fumarate reductase, that are easily oxidized by molecular oxygen (Imlay, 1995; Messner and Imlay, 2002).”
BackgroundSelf-citationHow Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway
Kumar, S. R., & Imlay, J. A. (2013) · Journal of Bacteriology · doi:10.1128/jb.00737-13 · Cited by 88
Self-citationFu, H., Yuan, J., & Gao, H. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.08.012 · Cited by 88
Response to oxidative stress in Paracoccidioides yeast cells as determined by proteomic analysis
Grossklaus, D. D. A., Bailão, A. M., de Rezende, T. C. V., Borges, C. L., de Oliveira, M. A. P., Parente, J. A., & Soares, C. M. D. A. (2013) · Microbes and Infection · doi:10.1016/j.micinf.2012.12.002 · Cited by 86
Huang, S., Braun, H., Gawryluk, R. M. R., & Millar, A. H. (2019) · The Plant Journal · doi:10.1111/tpj.14227 · Cited by 84
Mashruwala, A. A., Pang, Y. Y., Rosario‐Cruz, Z., Chahal, H. K., Benson, M. A., Mike, L. A., Skaar, E. P., Torres, V. J., Nauseef, W. M., & Boyd, J. M. (2015) · Molecular Microbiology · doi:10.1111/mmi.12860 · Cited by 79
“Respiratory molecules are a source of intracellular ROS (Messner and Imlay, 1999; 2002; Seaver and Imlay, 2004).”
Busch, A. W. U., & Montgomery, B. L. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.010 · Cited by 85
Kim, Y., Lee, Y., Kim, S. H., Yeom, J., Yeom, S., Kim, B. S., Oh, S., Park, S., Jeon, C. O., & Park, W. (2006) · PROTEOMICS · doi:10.1002/pmic.200600320 · Cited by 82
Nantapong, N., Murata, R., Trakulnaleamsai, S., Kataoka, N., Yakushi, T., & Matsushita, K. (2019) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-019-09848-2 · Cited by 81
Cytochrome bd Displays Significant Quinol Peroxidase Activity
Al-Attar, S., Yu, Y., Pinkse, M. W. H., Hoeser, J., Friedrich, T., Bald, D., & de Vries, S. (2016) · Scientific Reports · doi:10.1038/srep27631 · Cited by 80
Link Between Antibiotic Persistence and Antibiotic Resistance in Bacterial Pathogens
Eisenreich, W., Rudel, T., Heesemann, J., & Goebel, W. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.900848 · Cited by 89
Superoxide Destroys the [2Fe-2S]2+ Cluster of FNR from Escherichia coli
Sutton, V. R., Stubna, A., Patschkowski, T., Münck, E., Beinert, H., & Kiley, P. J. (2003) · Biochemistry · doi:10.1021/bi0357053 · Cited by 73
Thirupathi, A., & Pinho, R. A. (2018) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-018-0633-1 · Cited by 75
Lord, T., Martin, J. H., & Aitken, R. J. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.114.122820 · Cited by 71
“Covalent modification of SDHA within the oocyte’s mitochondria likely results in autooxidation and subsequent transference of electrons to oxygen rather than to coenzyme Q [47].”
BackgroundKluckova, 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
Energy depletion in seizures: Anaplerosis as a strategy for future therapies
Kovac, S., Abramov, A. Y., & Walker, M. C. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.05.012 · Cited by 71
Formation of ring-opened and rearranged products of guanine: Mechanisms and biological significance
Jena, N. R., & Mishra, P. C. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.04.008 · Cited by 70
Koju, N., Taleb, A., Zhou, J., Ge, L., Yang, J., Cao, X., Lei, H., & Ding, Q. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.11.128 · Cited by 72
Mashruwala, A. A., & Boyd, J. M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170283 · Cited by 69
A Rex Family Transcriptional Repressor Influences H 2 O 2 Accumulation by Enterococcus faecalis
Vesić, D., & Kristich, C. J. (2013) · Journal of Bacteriology · doi:10.1128/jb.02135-12 · Cited by 67
“coli can occur as a result of adventitious autoxidation by oxygen of flavin-containing enzymes, including fumarate reductase (42).”
BackgroundNew Challenges to Study Heterogeneity in Cancer Redox Metabolism
Benfeitas, R., Uhlén, M., Nielsen, J., & Mardinoğlu, A. (2017) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2017.00065 · Cited by 67
“They are produced intracellularly by several processes and dedicated enzymes, such as NADPH oxidases (Nauseef, 2008) and in multiple cellular compartments (Messner and Imlay, 2002; Chen et al., 2008; Murphy, 2009; Brown and Borutaite, 2012).”
BackgroundPleiotropic Role of Quorum-Sensing Autoinducer 2 inPhotorhabdus luminescens
Krin, E., Chakroun, N., Turlin, É., Givaudan, A., Gaboriau, F., Bonne, I., Rousselle, J.-C., Frangeul, L., Lacroix, C., Hullo, M.-F., et al. (2006) · Applied and Environmental Microbiology · doi:10.1128/aem.00398-06 · Cited by 64
Kôrge, P., John, S., Calmettes, G., & Weiss, J. N. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.768325 · Cited by 63
“coli strain KM5 (18), submitochondrial particles (SMP) from beef heart mitochondria (16), or mitochondria isolated from skeletal muscle (19).”
BackgroundThe Iron-Sulfur Clusters in Escherichia coli Succinate Dehydrogenase Direct Electron Flow
Cheng, V. W. T., Ma, E., Zhao, Z., Rothery, R. A., & Weiner, J. H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604900200 · Cited by 62
Tellurite-mediated disabling of [4Fe–4S] clusters of Escherichia coli dehydratases
Calderón, I. L., Elías, A. O., Fuentes, E. L., Pradenas, G. A., Castro, M. E., Arenas, F., Pérez, J. M., & Vásquez, C. C. (2009) · Microbiology · doi:10.1099/mic.0.026260-0 · Cited by 62
Metadata
- Authors
- Messner, K. R., & Imlay, J. A.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Imlay, James A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 277
- Issue
- 45
- Pages
- 42563-42571
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2044412059
- Cited by
- 301
- References
- 57
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 12 · 2023: 11 · 2022: 15 · 2021: 14 · 2020: 18 · 2019: 13 · 2018: 17 · 2017: 14 · 2016: 8 · 2015: 12 · 2014: 16 · 2013: 21 · 2012: 18
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM49640)
- National Institute of General Medical Sciences (R01GM049640, GM 49640, T32 GM07283-20, T32GM007283)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Keywords
- fumarate reductase, succinate dehydrogenase, superoxide production, hydrogen peroxide production, FAD, flavin semiquinone, [2Fe-2S] cluster, oxidative stress, Escherichia coli
- MeSH terms
- Amino Acid Oxidoreductases, Cell Line, Cell Membrane, Escherichia coli, Flavin-Adenine Dinucleotide, Hydrogen Peroxide, Iron-Sulfur Proteins, Kinetics, Oxidation-Reduction, Solvents, Succinate Dehydrogenase, Superoxides, D-Aspartate Oxidase
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