Cited by 329Mitochondrial Function and PathologyRedox biology and oxidative stressExercise and Physiological Responses

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Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise

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Goncalves, Renata L.S., Quinlan, Casey L., Perevoshchikova, Irina V., Hey-Mogensen, Martin, Brand, Martin D.·2015·Journal of Biological Chemistry

DOI 10.1074/jbc.m114.619072PMC PMC4281723

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Abstract

The sites and rates of mitochondrial production of superoxide and H 2 O 2 in vivo are not yet defined. At least 10 different mitochondrial sites can generate these species. Each site has a different maximum capacity ( e.g. the outer quinol site in complex III (site III Qo ) has a very high capacity in rat skeletal muscle mitochondria, whereas the flavin site in complex I (site I F ) has a very low capacity). The maximum capacities can greatly exceed the actual rates observed in the absence of electron transport chain inhibitors, so maximum capacities are a poor guide to actual rates. Here, we use new approaches to measure the rates at which different mitochondrial sites produce superoxide/H 2 O 2 using isolated muscle mitochondria incubated in media mimicking the cytoplasmic substrate and effector mix of skeletal muscle during rest and exercise. We find that four or five sites dominate during rest in this ex vivo system. Remarkably, the quinol site in complex I (site I Q ) and the flavin site in complex II (site II F ) each account for about a quarter of the total measured rate of H 2 O 2 production. Site I F , site III Qo , and perhaps site E F in the β-oxidation pathway account for most of the remainder. Under conditions mimicking mild and intense aerobic exercise, total production is much less, and the low capacity site I F dominates. These results give novel insights into which mitochondrial sites may produce superoxide/H 2 O 2 in vivo .Ten mitochondrial sites of superoxide/H 2 O 2 generation are known, but their contributions in vivo are undefined. Results We assessed their rates ex vivo in conditions mimicking rest and exercise. Conclusion Sites I Q and II F generated half the signal at rest. During exercise, rates were lower, and site I F dominated. Significance Contributing sites ex vivo probably reflect those in vivo .

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How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
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
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388
Mitochondrial free radical generation, oxidative stress, and aging
Cadenas, E., & Davies, K. J. A. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00317-8 · Cited by 3,010
The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen
Boveris, A., & Chance, B. (1973) · Biochemical Journal · doi:10.1042/bj1340707 · Cited by 2,626
Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production
Powers, S. K., & Jackson, M. J. (2008) · Physiological Reviews · doi:10.1152/physrev.00031.2007 · Cited by 2,459
Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?
Halliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238
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Koves, T. R., Ussher, J. R., Noland, R. C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J. R. B., Newgard, C. B., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.013 · Cited by 1,990
Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926

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Background
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Mancini, M. C., McCall, C. P., Noland, R. C., Dantas, W. S., & Heden, T. D. (2025) · Oncogenesis · doi:10.1038/s41389-025-00593-y · Cited by 3
“The serum was aliquoted into a new tube and stored at − 80 °C until analysis.”
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Casuso, R. A. (2024) · Obesity Reviews · doi:10.1111/obr.13794 · Cited by 3
“48 It should be noted that if RET decreases the amount of CI, there would be more Q pool dedicated to FADH 2 pathways, which would enhance FAO.”
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Aparicio‐Trejo, O. E., Tapia, E., Briones‐Herrera, A., Martínez‐Klimova, E., & Pedraza‐Chaverrí, J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819621-2.00027-9 · Cited by 3
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Guimarães, T. T., da Silva, D. C. A., Pinto, E. C. D. S., Rubini, E. D. C., de Amorim, M. V. C., Dutra, P. M. L., Borges, R. M., Cevada, T., & Coelho, W. S. (2022) · Brazilian Journals Editora eBooks · doi:10.35587/brj.ed.0001379 · Cited by 3
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Zhang, Y., Chen, Y., & Zhao, S. (2022) · Molecular & Cellular Toxicology · doi:10.1007/s13273-022-00313-2 · Cited by 3
“…cells in Bupivacaine 13.3 μmol/L + Isoprenaline 5.0 nmol/L. Bupivacaine+ISO-S contracting cells in Bupivacaine 13.3 μmol/L + Isoprenaline 5.0 nmol/L of ROS due to proton leakage occurs under normal respiratory conditions, but can be greatly enhanced in response to stress (Goncalves et al. 2015).”
Influential
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Heiat, F. (2017) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 3
Impact of Lifestyle and Clinical Interventions on Mitochondrial Function in Obesity and Type 2 Diabetes
Osborne, B., Brandon, A. E., Smith, G. C., & Turner, N. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811752-1.00016-x · Cited by 3
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Mihanovic, I., Marinović, J., Bulat, C., Lukšić, B., Marović, Z., & Ljubković, M. (2026) · Cells · doi:10.3390/cells15090830 · Cited by 2
“…of H 2 O 2 production was multiplied by 2 (since 2 electrons are required for partial reduction of oxygen to H 2 O 2 ), and this value was divided by total concomitant oxygen consumption (LEAK CI + CII) multiplied by 4 (reflecting the 4 electrons needed for complete O 2 reduction to water) [32].”
Does high mitochondrial efficiency carry an oxidative cost? The case of the African pygmy mouse (Mus mattheyi)
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Yasul, Y., Yılmaz, B., Şenel, Ö., Kurt, D., Akbulut, T., Çalıkuşu, A., Anadol, E., & Yılmaz, C. (2025) · European Journal of Applied Physiology · doi:10.1007/s00421-025-05756-8 · Cited by 1
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Huertas, J. R., Aragón‐Vela, J., Andersen, A. B., Bejder, J., Nybo, L., Nordsborg, N. B., Rodríguez‐Carrillo, A., Enriquez, J. A., Cogliati, S., & Casuso, R. A. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117217 · Cited by 1
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BackgroundMethodInfluential
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Mohan, M., Rafi, S. T. M., Muthusami, S., Ramalingam, S., Sambandam, Y., Selvendiran, K., Ramachandran, I., & Kumaran, R. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-5422-0_216 · Cited by 1
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Sofla, M. A. S., & Nikseresht, A. (2022) · مجله علمی پزشکی جندی شاپور · doi:10.32598/jsmj.21.5.2498 · Cited by 1
Resveratrol slows cell growth by targeting the Warburg effect and stimulating mitochondria metabolism
Fonseca, J. (2019) · Brock University Digital Repository (Brock University)
Disturbances in Energy Supply
Arnhold, J. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816388-7.00004-8
An unexpected lack of difference in superoxide/H 2 O 2 production rates in isolated heart and skeletal muscle mitochondria from a mouse model of Barth SyndromePreprint
Gonçalves, R. L. S., Schlame, M., Bartelt, A., Brand, M. D., & Hotamışlıgil, G. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.07.083105
“31. Dudek, J., Cheng, I. F., Balleininger, M., Vaz, F. M., Streckfuss-Bömeke, K., Hübscher, D., Vukotic, M., Wanders, R. J. A., Rehling, P., and Guan, K. (2013) Cardiolipin deficiency affects respiratory chain function and organization in an induced pluripotent stem cell model of Barth syndrome.”
BackgroundInfluential
Thioredoxin reductase controls the capacity of peroxiredoxins to limit mitochondrial H 2 O 2 releasePreprint
Hoehne, M. N., Jacobs, L. H. C., Lapacz, K. J., Murschall, L. M., Marker, T., Morgan, B., Fricker, M. D., Belousov, V. V., & Riemer, J. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.08.451718
Carbon nanodots (CNDs): tuning structures and functions in oxidative radical interactions
Ji, Z. (2020) · NC Digital Online Collection of Knowledge and Scholarship (The University of North Carolina at Greensboro)
Mitochondrial metabolism and carcinogenesis
Aras, S., Purandare, N., & Grossman, L. I. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822416-8.00001-4
VARIABILIDADE DA FREQUÊNCIA CARDÍACA
Rubini, E. D. C. (2022) · Brazilian Journals Editora eBooks · doi:10.35587/brj.ed.0001385
TÓPICOS ESPECIAIS: METABOLÔMICA
Borges, R. M. (2022) · Brazilian Journals Editora eBooks · doi:10.35587/brj.ed.0001387
ORIGEM DO OVERTRAINING: ESTRESSE OXIDATIVO
Coelho, W. S. (2022) · Brazilian Journals Editora eBooks · doi:10.35587/brj.ed.0001383
OVERTRAINING NO FISICULTURISMO
de Amorim, M. V. C. (2022) · Brazilian Journals Editora eBooks · doi:10.35587/brj.ed.0001380
Targeting Tumors Through Enhancers of Oxidative Stress
Kapur, A., Sharma, S. T., & Patankar, M. S. (2022) · Handbook of Oxidative Stress in Cancer: Therapeutic Aspects · doi:10.1007/978-981-16-1247-3_164-1

Authors: Goncalves, R. L. S., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M., & Brand, M. D.
Affiliations: Buck Institute for Research on Aging (US)
Corresponding author: Goncalves, Renata L.S.
Perevoshchikova, Irina V.
Brand, Martin D.
ORCID: Goncalves, Renata L.S.
Quinlan, Casey L.
Brand, Martin D.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2015-01
Volume: 290
Issue: 1
Pages: 209-227
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m114.619072
PMC: PMC4281723
OpenAlex: W2087350238
Cited by: 329
References: 162
Citations by year: 2026: 15 · 2025: 17 · 2024: 23 · 2023: 30 · 2022: 40 · 2021: 30 · 2020: 33 · 2019: 39 · 2018: 27 · 2017: 34 · 2016: 20 · 2015: 21
FWCI: 10.24
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 2102 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (TL1 AG032116)
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
Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
Keywords: superoxide production, hydrogen peroxide production, skeletal muscle mitochondria, mitochondrial electron transport chain, fatty acid beta-oxidation, physical activity, rest, reactive oxygen species, isolated mitochondria
MeSH terms: Animals, Female, Hydrogen Peroxide, Malates, Mitochondria, Muscle, Oligomycins, Oxygen Consumption, Physical Conditioning, Animal, Rest, Superoxides, Uncoupling Agents, Rats, Wistar, Muscle, Skeletal, Succinic Acid, Electron Transport Complex II, Electron Transport Complex I, Cytochromes b, Tissue Culture Techniques, Rats

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Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise

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