Cited by 1,260Mitochondrial Function and PathologyRedox biology and oxidative stressCoenzyme Q10 studies and effects

Generation of reactive oxygen species by the mitochondrial electron transport chain

Liu, Yuanbin, Fiskum, Gary, Schubert, David·2002·Journal of Neurochemistry

Abstract

Generation of reactive oxygen species (ROS) by the mitochondrial electron transport chain (ETC), which is composed of four multiprotein complexes named complex I-IV, is believed to be important in the aging process and in the pathogenesis of neurodegenerative diseases such as Parkinson's disease. Previous studies have identified the ubiquinone of complex III and an unknown component of complex I as the major sites of ROS generation. Here we show that the physiologically relevant ROS generation supported by the complex II substrate succinate occurs at the flavin mononucleotide group (FMN) of complex I through reversed electron transfer, not at the ubiquinone of complex III as commonly believed. Indirect evidence indicates that the unknown ROS-generating site within complex I is also likely to be the FMN group. It is therefore suggested that the major physiologically and pathologically relevant ROS-generating site in mitochondria is limited to the FMN group of complex I. These new insights clarify an elusive target for intervening mitochondrial ROS-related processes or diseases.

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Crossref · 10.1046/j.0022-3042.2002.00744.x

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Authors
Liu, Y., Fiskum, G., & Schubert, D.
Affiliations
  • Salk Institute for Biological Studies (US)
  • University of Maryland, Baltimore (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2002-03
Volume
80
Issue
5
Pages
780-787
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2036127346
Cited by
1,260
References
31
Citations by year
2026: 17 · 2025: 29 · 2024: 38 · 2023: 34 · 2022: 46 · 2021: 71 · 2020: 69 · 2019: 67 · 2018: 61 · 2017: 49 · 2016: 63 · 2015: 50 · 2014: 73 · 2013: 53 · 2012: 65
FWCI
16.15
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Keywords
reactive oxygen species, mitochondrial electron transport chain, complex I, flavin mononucleotide, succinic acid, coenzyme Q10, cytochrome bc1 complex, aging, Parkinson's disease, neurodegenerative diseases
MeSH terms
Aging, Animals, Brain Chemistry, Electron Transport, Flavin Mononucleotide, Hydrogen Peroxide, Mitochondria, NADH, NADPH Oxidoreductases, Oxidation-Reduction, Subcellular Fractions, Electron Transport Complex III, Ubiquinone, Reactive Oxygen Species, Electron Transport Complex I, Rats

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