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The Role of Mitochondria in Reactive Oxygen Species Metabolism and Signaling
Open accessAbstract
Oxidative stress is considered a major contributor to the etiology of both “normal” senescence and severe pathologies with serious public health implications. Several cellular sources, including mitochondria, are known to produce significant amounts of reactive oxygen species (ROS) that may contribute to intracellular oxidative stress. Mitochondria possess at least 10 known sites that are capable of generating ROS, but they also feature a sophisticated multilayered ROS defense system that is much less studied. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal at the level of mitochondria. An integrative systemic approach is applied to analysis of mitochondrial ROS metabolism, which is “dissected” into ROS generation, ROS emission, and ROS scavenging. The in vitro ROS‐producing capacity of several mitochondrial sites is compared in the metabolic context and the role of mitochondria in ROS‐dependent intracellular signaling is discussed.
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“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'.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [22]
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“The highly effective mitochondrial antioxidative defense system encompasses the thioredoxin/peroxiredoxin system as well as the glutathione/glutathione peroxidase system (overview in [22,117]).”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [22]
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Citations
Cites
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269
McCord, J. M., & Fridovich, I. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63504-5 · Cited by 12,952
Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Hydroperoxide metabolism in mammalian organs.
Chance, B., Sies, H., & Boveris, A. (1979) · Physiological Reviews · doi:10.1152/physrev.1979.59.3.527 · Cited by 5,827
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084
Boveris, A., & Chance, B. (1973) · Biochemical Journal · doi:10.1042/bj1340707 · Cited by 2,626
Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria
Turrens, J. F., & Boveris, A. (1980) · Biochemical Journal · doi:10.1042/bj1910421 · Cited by 1,601
Role of reactive oxygen species in the pathophysiology of human reproduction.
Agarwal, A., Saleh, R., & Bedaiwy, M. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(02)04948-8 · Cited by 1,578
Oxygen, oxidative stress, hypoxia, and heart failure
Giordano, F. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24408 · Cited by 1,515
Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?
Giorgio, M., Trinei, M., Migliaccio, E., & Pelicci, P. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2240 · Cited by 1,473
Sawyer, D. T., & Valentine, J. S. (1981) · Accounts of Chemical Research · doi:10.1021/ar00072a005 · Cited by 1,365
Mitochondrial metabolism of reactive oxygen species
Andreyev, A. Y., Kushnareva, Y. E., & Starkov, A. A. (2005) · Biochemistry (Moscow) · doi:10.1007/s10541-005-0102-7 · Cited by 1,336
Self-citationSubcellular Distribution of Superoxide Dismutases (SOD) in Rat Liver
Okado‐Matsumoto, A., & Fridovich, I. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105395200 · Cited by 1,036
Reactive oxygen species in tumor progression
Peter, S. F. (2005) · Frontiers in bioscience · doi:10.2741/1667 · Cited by 972
Mitochondria take center stage in aging and neurodegeneration
Beal, M. F. (2005) · Annals of Neurology · doi:10.1002/ana.20624 · Cited by 957
Wardman, P. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.06.026 · Cited by 875
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 711
Self-citationSkulachev, V. P. (1996) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500005795 · Cited by 703
Newsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira‐Emilio, H. C., Carpinelli, A. R., & Curi, R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135871 · Cited by 684
Bioenergetics and the formation of mitochondrial reactive oxygen species
Ádám‐Vizi, V., & Chinopoulos, C. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.10.005 · Cited by 623
Ho, Y., Magnenat, J.-L., Bronson, R. T., Cao, J., Gargano, M. D., Sugawara, M., & Funk, C. D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16644 · Cited by 562
Origin and turnover of mitochondrial glutathione.
Griffith, O. W., & Meister, A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.14.4668 · Cited by 500
Oxidative stress and aberrant signaling in aging and cognitive decline
Dröge, W., & Schipper, H. M. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00294.x · Cited by 479
LAMBERT, A. J., & BRAND, M. D. (2004) · Biochemical Journal · doi:10.1042/bj20040485 · Cited by 470
Superoxide Radical and Iron Modulate Aconitase Activity in Mammalian Cells
Gardner, P. R., Raineri, I., Epstein, L. B., & White, C. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.22.13399 · Cited by 469
Role of mitochondrial DNA in toxic responses to oxidative stress
Houten, B. V., Woshner, V. M., & Santos, J. H. (2005) · DNA repair · doi:10.1016/j.dnarep.2005.03.002 · Cited by 461
Insulin, ketone bodies, and mitochondrial energy transduction
Sato, K., Kashiwaya, Y., Keon, C. A., Tsuchiya, N., King, M. T., Radda, G. K., Chance, B., Clarke, K., & Veech, R. L. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.8.7768357 · Cited by 455
Generation of Reactive Oxygen Species in the Reaction Catalyzed by α-Ketoglutarate Dehydrogenase
Tretter, L., & Ádám‐Vizi, V. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1842-04.2004 · Cited by 455
Reactive Oxygen Species in Mitochondria-Mediated Cell Death
Orrenius, S. (2007) · Drug Metabolism Reviews · doi:10.1080/03602530701468516 · Cited by 431
Hackenbrock, C. R., Chazotte, B., & Gupte, S. S. (1986) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf00743010 · Cited by 384
Mitochondrial membrane potential and aging
Nicholls, D. G. (2003) · Aging Cell · doi:10.1111/j.1474-9728.2003.00079.x · Cited by 351
Hyslop, P. A., Zhang, Z., Pearson, D. V., & Phebus, L. A. (1995) · Brain Research · doi:10.1016/0006-8993(94)01291-o · Cited by 338
Takeshige, K., & Minakami, S. (1979) · Biochemical Journal · doi:10.1042/bj1800129 · Cited by 299
Are mitochondria critical in the pathogenesis of Alzheimer's disease?
Reddy, P. H., & Beal, M. F. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.03.004 · Cited by 294
Beal, M. F. (2004) · Journal of Bioenergetics and Biomembranes · doi:10.1023/b:jobb.0000041772.74810.92 · Cited by 277
Intracellular diffusion gradients of O2 and ATP
Jones, D. P. (1986) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1986.250.5.c663 · Cited by 268
Oxidative Stress in Allergic and Inflammatory Skin Diseases
Okayama, Y. (2005) · Current Drug Targets - Inflammation & Allergy · doi:10.2174/1568010054526386 · Cited by 265
Role of Reactive Oxygen Species in Skin Carcinogenesis
Nishigori, C., Hattori, Y., & Toyokuni, S. (2004) · Antioxidants and Redox Signaling · doi:10.1089/152308604773934314 · Cited by 260
Effects of age and caloric restriction on glutathione redox state in mice
Rebrin, I., Kamzalov, S., & Sohal, R. S. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00388-5 · Cited by 243
Tissue heterogeneity of the mammalian mitochondrial proteome
Johnson, D., Harris, R. A., French, S. A., Blair, P. V., You, J., Bemis, K. G., Wang, M., & Balaban, R. S. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00108.2006 · Cited by 209
Wahlländer, A., Soboll, S., Sies, H., Linke, I. M., & Monika, M. (1979) · FEBS Letters · doi:10.1016/0014-5793(79)80069-1 · Cited by 189
J.Kim, G., Chandrasekaran, K., & Morgan, W. F. (2006) · Mutagenesis · doi:10.1093/mutage/gel048 · Cited by 181
Gibson, G. E., Blass, J. P., Beal, M. F., & Bunik, V. I. (2005) · Molecular Neurobiology · doi:10.1385/mn:31:1-3:043 · Cited by 181
Hoffman, D. L., Salter, J. D., & Brookes, P. S. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00699.2006 · Cited by 165
Cheng, W., Ho, Y., Ross, D. A., Valentine, B. A., Combs, G. F., & Lei, X. G. (1997) · Journal of Nutrition · doi:10.1093/jn/127.8.1445 · Cited by 159
Hyperoxia increases H2O2 production by brain in vivo
Yusa, T., Beckman, J. S., Crapo, J. D., & Freeman, B. Α. (1987) · Journal of Applied Physiology · doi:10.1152/jappl.1987.63.1.353 · Cited by 156
Chinopoulos, C., Tretter, L., & Ádám‐Vizi, V. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0730220.x · Cited by 155
Burkitt, M. J., & Wardman, P. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4578 · Cited by 155
WILLIAMSON, J. R., & Corkey, B. E. (1979) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(79)55025-3 · Cited by 153
Carothers, D. J., Pons, G., & Patel, M. S. (1989) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(89)90309-3 · Cited by 151
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
Ohashi, T., Mizutani, A., Murakami, A., Kojo, S., Ishii, T., & Taketani, S. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03262-8 · Cited by 143
Mitochondrial Oxidative Stress and Mitochondrial DNA
Kang, D., & Hamasaki, N. (2003) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2003.195 · Cited by 140
Mitochondrial targeting of quinones: Therapeutic implications
Cochemé, H. M., Kelso, G. F., James, A. M., Ross, M. F., Trnka, J., Mahendiran, T., Asin-Cayuela, J., Blaikie, F. H., Manas, A. B., Porteous, C. M., et al. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.02.007 · Cited by 138
Liu, J., & Ames, B. N. (2005) · Nutritional Neuroscience · doi:10.1080/10284150500047161 · Cited by 138
The Effective Proton Conductance of the Inner Membrane of Mitochondria from Brown Adipose Tissue
Nicholls, D. G. (1977) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1977.tb11674.x · Cited by 135
Myxothiazol Induces H2O2 Production from Mitochondrial Respiratory Chain
Starkov, A. A., & Fiskum, G. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4409 · Cited by 133
Self-citationRespiration-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
Succinate accumulation in man during exercise
Hochachka, P. W., & Dressendorfer, R. H. (1976) · European Journal of Applied Physiology · doi:10.1007/bf00423282 · Cited by 125
Staniek, K., & Nohl, H. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(99)00083-3 · Cited by 124
Mitochondrial dysfunction and amyotrophic lateral sclerosis
Hervías, I., Beal, M. F., & Manfredi, G. (2005) · Muscle & Nerve · doi:10.1002/mus.20489 · Cited by 122
Schiller, J., Fuchs, B., Arnhold, J., & Arnold, K. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033456828 · Cited by 121
The antioxidant functions of cytochrome c
Korshunov, S., Krasnikov, B. F., PEREVERZEV, M. O., & Skulachev, V. P. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01525-2 · Cited by 118
Vogel, R., Wiesinger, H., Hamprecht, B., & Dringen, R. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00748-x · Cited by 115
Oxidative Stress as the Leading Cause of Acute Myocardial Infarction in Diabetics
Filippo, C. D., Cuzzocrea, S., Rossi, F., Marfella, R., & D’Amico, M. (2006) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2006.00077.x · Cited by 111
The role of manganese superoxide dismutase in health and disease
Robinson, B. H. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005427323835 · Cited by 110
OXYGEN, GENE EXPRESSION, AND CELLULAR FUNCTION
Samson, F. E. (1997) · Shock · doi:10.1097/00024382-199711000-00014 · Cited by 108
Functional consequences of mitochondrial proteome heterogeneity
Johnson, D., Harris, R. A., Blair, P. V., & Balaban, R. S. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00109.2006 · Cited by 108
Rebrin, I., & Sohal, R. S. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.08.014 · Cited by 100
Mitochondrial DNA repair: A critical player in the response of cells of the CNS to genotoxic insults
LeDoux, S. P., Druzhyna, N. M., Hollensworth, S. B., Harrison, J., & Wilson, G. L. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.10.002 · Cited by 85
Guidot, D. M., Repine, J. E., Kitlowski, A. D., Flores, S. C., Nelson, S. K., Wright, R. M., & McCord, J. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118100 · Cited by 82
The inhibition of succinate dehydrogenase by oxaloacetate
Wojtczak, L., Wojtczak, A., & Ernster, L. (1969) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(69)90310-6 · Cited by 70
Afanasʹev, I. B. (2007) · Molecular Biotechnology · doi:10.1007/s12033-007-0056-7 · Cited by 68
Zoccarato, F., Cavallini, L., Bortolami, S., & Alexandre, A. (2007) · Biochemical Journal · doi:10.1042/bj20070215 · Cited by 66
Redox activation of mitochondrial intermembrane space Cu,Zn-superoxide dismutase
Iñarrea, P., Moini, H., Rettori, D., Han, D., MARTÍNEZ, J., García‐Rubio, I., Fernández‐Vizarra, E., Iturralde, M., & Cadenas, E. (2005) · Biochemical Journal · doi:10.1042/bj20041683 · Cited by 59
Superoxide radical as electron donor for oxidative phosphorylation of ADP
Mailer, K. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91240-s · Cited by 55
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
Protein-mediated energy-dissipating pathways in mitochondria
Starkov, A. A. (2006) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2006.08.015 · Cited by 40
Self-citationCytochrome P-450, Reductive Metabolism, And Cell Injury
de GROOT, H., & Sies, H. (1989) · Drug Metabolism Reviews · doi:10.3109/03602538909103543 · Cited by 36
Effect of ammonia on mitochondrial and cytosolic NADH and NADPH systems in isolated rat liver cells
Tischler, M. E., Hecht, P., & WILLIAMSON, J. R. (1977) · FEBS Letters · doi:10.1016/0014-5793(77)80129-4 · Cited by 33
The inhibition of succinate dehydrogenase by oxaloacetate
Zeylemaker, W. P., & Slater, E. C. (1967) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(67)90214-8 · Cited by 32
Relationships between γ‐aminobutyrate and succinate cycles during and after cerebral ischemia
Benzi, G., Pastoris, O., & Dossena, M. (1982) · Journal of Neuroscience Research · doi:10.1002/jnr.490070210 · Cited by 26
Burkitt, M. J., Jones, C. M., Lawrence, A. D., & Wardman, P. (2004) · Biochemical Society Symposia · doi:10.1042/bss0710097 · Cited by 14
Myocardial metabolic markers of total ischemia in vitro.
Kakinuma, Y., Matsubara, T., Hashimoto, T., & Sakamoto, N. (1994) · PubMed · doi:10.18999/nagjms.57.1-2.35 · Cited by 13
Skulachev, V. P. (1996) · PubMed · Cited by 12
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Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases
Phaniendra, A., Jestadi, D. B., & Periyasamy, L. (2015) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-014-0446-0 · Cited by 2,886
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Granger, D. N., & Kvietys, P. R. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.020 · Cited by 1,550
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Metadata
- Authors
- Starkov, A. A.
- Affiliations
- Cornell University (US)
- Corresponding author
- Starkov, Anatoly A.
- ORCID
- Starkov, Anatoly A.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2008-12
- Volume
- 1147
- Issue
- 1
- Pages
- 37-52
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC2869479
- OpenAlex
- W2053022803
- Cited by
- 846
- References
- 86
- Citations by year
- 2026: 39 · 2025: 39 · 2024: 42 · 2023: 66 · 2022: 67 · 2021: 78 · 2020: 74 · 2019: 55 · 2018: 42 · 2017: 46 · 2016: 50 · 2015: 39 · 2014: 38 · 2013: 41 · 2012: 39
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG014930, P01AG014930)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondria, reactive oxygen species, oxidative stress, ROS signaling, reactive oxygen species scavenging, aging, cellular senescence
- MeSH terms
- Humans, Mitochondria, Signal Transduction, Reactive Oxygen Species, Oxidative Stress
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