The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
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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BackgroundThe Free Radical Theory of Aging Matures
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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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