Cited by 470Mitochondrial Function and PathologyCoenzyme Q10 studies and effectsRedox biology and oxidative stress

Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane

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LAMBERT, Adrian J., BRAND, Martin D.·2004·Biochemical Journal

Abstract

The relationship between protonmotive force and superoxide production by mitochondria is poorly understood. To address this issue, the rate of superoxide production from complex I of rat skeletal muscle mitochondria incubated under a variety of conditions was assessed. By far, the largest rate of superoxide production was from mitochondria respiring on succinate; this rate was almost abolished by rotenone or piericidin, indicating that superoxide production from complex I is large under conditions of reverse electron transport. The high rate of superoxide production by complex I could also be abolished by uncoupler, confirming that superoxide production is sensitive to protonmotive force. It was inhibited by nigericin, suggesting that it is more dependent on the pH gradient across the mitochondrial inner membrane than on the membrane potential. These effects were examined in detail, leading to the conclusions that the effect of protonmotive force was mostly direct, and not indirect through changes in the redox state of the ubiquinone pool, and that the production of superoxide by complex I during reverse electron transport was at least 3-fold more sensitive to the pH gradient than to the membrane potential.

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Authors
LAMBERT, A. J., & BRAND, M. D.
Affiliations
MRC Mitochondrial Biology Unit (GB)
Venue
Biochemical Journal
Published
2004-08-24
Volume
382
Issue
2
Pages
511-517
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2035127779
Cited by
470
References
52
Citations by year
2026: 8 · 2025: 13 · 2024: 14 · 2023: 16 · 2022: 16 · 2021: 27 · 2020: 15 · 2019: 24 · 2018: 26 · 2017: 20 · 2016: 19 · 2015: 31 · 2014: 28 · 2013: 26 · 2012: 28
FWCI
7.93
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
superoxide production, complex I, mitochondrial respiration, proton motive force, pH gradient, inner mitochondrial membrane, reverse electron transfer, succinic acid, rotenone, piericidins, nigericin, membrane potential, skeletal muscle mitochondria, uncouplers
MeSH terms
Animals, Female, Hydrogen Peroxide, Hydrogen-Ion Concentration, Intracellular Membranes, Mitochondria, Mitochondria, Muscle, Superoxides, Rats, Wistar, Muscle, Skeletal, Electron Transport Complex I, Rats

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