Cited by 447Mitochondrial Function and PathologyRedox biology and oxidative stressNitric Oxide and Endothelin Effects

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Dependence of H2O2 Formation by Rat Heart Mitochondria on Substrate Availability and Donor Age

Hansford, Richard G., Hogue, Barbara A., Mildaziene, Vida·1997·Journal of Bioenergetics and Biomembranes

DOI 10.1023/a:1022420007908

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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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Influential
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Authors: Hansford, R. G., Hogue, B. A., & Mildaziene, V.
Affiliations: National Institute on Aging (US)
Venue: Journal of Bioenergetics and Biomembranes
Publisher: Springer Science and Business Media LLC
Published: 1997-02
Volume: 29
Issue: 1
Pages: 89-95
ISSN: 0145-479X (ISSN-L)
1573-6881
DOI: 10.1023/a:1022420007908
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Dependence of H2O2 Formation by Rat Heart Mitochondria on Substrate Availability and Donor Age

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