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Dependence of H2O2 Formation by Rat Heart Mitochondria on Substrate Availability and Donor Age
Abstract
We have examined the substrate specificity and inhibitor sensitivity of H2O2 formation by rat heart mitochondria. Active H2O2 production requires both a high fractional reduction of Complex I (indexed by NADH/NAD+ + NADH ratio) and a high membrane potential, delta psi. These conditions are achieved with supraphysiological concentrations of succinate. With physiological concentrations of NAD-linked substrates, rates of H2O2 formation are much lower (less than 0.1% of respiratory chain electron flux) but may be stimulated by the Complex III inhibitor antimycin A, but not by myxothiazol. Addition of Mn2+ to give 10 nmol/mg of mitochondrial protein enhances H2O2 production with all substrate combinations, possibly by repleting mitochondrial superoxide dismutase with this cation. Contrary to previously published work, no increased activity of H2O2 production was found with heart mitochondria from senescent (24 month) rats, relative to young adults (6 month).
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“Δψm is an important factor for maintaining cellular energy homeostasis, and small reductions in Δψm induced by mild uncoupling were shown to decrease H2O2 emissions (51,52) and produce a natural antioxidant effect (53).”
From TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet–Induced Insulin Resistance in Skeletal Muscle (2019) · cites this paper as [51]
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Dolci, G. S., Rosa, H. Z., Barcelos, R. C. S., Vey, L. T., dos Santos, A. C., DallaVechia, P., Bizzi, C. A., da Cunha, M. A., Baldisserotto, B., & Bürger, M. E. (2016) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2016.09.005 · Cited by 4
Pine, M. D., Greer, K. A., & Busbee, D. L. (2007) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2007.02.005 · Cited by 4
Slater, P. G., Domínguez-Romero, M. E., Campos, G., Aravena, V., Cavieres-Lepe, J., & Eisner, V. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1529093 · Cited by 4
“Both mitochondrial calcium uptake during excitotoxicity (Stout et al., 1998) and ROS production (Hansford et al., 1997), depend on mitochondrial membrane potential.”
Saarti, M., Almukhtar, H. M., Smith, P. A., & Roberts, R. E. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.173917 · Cited by 3
Mitochondrial Reactive Oxygen Species Production Mediated by Romo1 Expression
Yoo, Y. D. (2013) · Hanyang Medical Reviews · doi:10.7599/hmr.2013.33.2.90 · Cited by 3
Calorie Restriction: A Potent Mechanistic Solution to the Oxygen Paradox
Yu, B., Lee, D. Y., Hwang, E. H., & Lim, B. O. (1999) · Springer eBooks · doi:10.1007/978-3-642-60100-2_8 · Cited by 3
Apoptosis in the overloaded myocardium: potential stimuli and modifying signals
Schumann, H., Heinrich, H., Bartling, B., Darmer, D., & Holtz, J. (2000) · Steinkopff eBooks · doi:10.1007/978-3-642-57724-6_4 · Cited by 3
Cytopathological Mechanisms in Mitochondrial Disease
Francione, L. M., & Fisher, P. R. (2010) · Current Chemical Biology · doi:10.2174/2212796811004010032 · Cited by 3
Fathi, M., & Mardani, P. (2024) · Agricultural sciences. · doi:10.5772/intechopen.1005612 · Cited by 2
Barron, M. J., & Turnbull, D. M. (2003) · Springer eBooks · doi:10.1007/978-94-017-0667-4_7 · Cited by 2
Mitochondria: Ultrastructure, dynamics, biogenesis, and main functions
Rigoulet, M., Bouchez, C. L., Molinié, T., Cuvellier, S., Mazat, J., Ransac, S., Duvezin‐Caubet, S., Paumard, P., & Devin, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821562-3.00025-3 · Cited by 3
Oxidative Stress, Dietary Restriction and Aging
Merry, B. J., & Ash, C. (2010) · Springer eBooks · doi:10.1007/978-90-481-8556-6_8 · Cited by 2
Haemostatic products as a potential therapy for vesicant-contaminated wounds
Hall, C. A. (2012) · University of Birmingham Institutional Research Archive (University of Birmingham) · Cited by 2
Caloric Restriction and Oxidative Stress
Škrha, J. (2011) · Wiley eBooks · doi:10.1002/9781118148143.ch6 · Cited by 2
The role of oxidative stress in C. elegans aging
Thamsen, M. (2011) · Gutenberg Open Science · doi:10.25358/openscience-4772 · Cited by 2
Metadata
- Authors
- Hansford, R. G., Hogue, B. A., & Mildaziene, V.
- Affiliations
- National Institute on Aging (US)
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 1997-02
- Volume
- 29
- Issue
- 1
- Pages
- 89-95
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W2414123687
- Cited by
- 447
- References
- 26
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 2 · 2022: 12 · 2021: 11 · 2020: 10 · 2019: 15 · 2018: 13 · 2017: 11 · 2016: 11 · 2015: 11 · 2014: 26 · 2013: 17 · 2012: 28
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- Lithuanian University of Health Sciences (submittedVersion)
- 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) › Nitric Oxide and Endothelin Effects
- Keywords
- hydrogen peroxide production, heart mitochondria, mitochondrial reactive oxygen species, complex I, NAD+/NADH ratio, membrane potential, succinic acid, antimycin A, myxothiazol, manganese, superoxide dismutase, donor age, senescence, substrate specificity, inhibitor sensitivity
- MeSH terms
- Aging, Animals, Electron Transport, Hydrogen Peroxide, Mitochondria, Heart, Substrate Specificity, Succinates, Uncoupling Agents, Rats
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.