Generation of reactive oxygen species by the mitochondrial electron transport chain
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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Under conditions of reverse electron transfer, inhibiting complex II lowers complex I-related ROS generation.
“Under these conditions inhibition of complex II leads to a reduction of complex I related ROS generation [15,16,19,20,24].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [19]
Complex II inhibitors that bind the dicarboxylate site or the Qp site attenuate ROS production when succinate is the prevalent substrate.
“The ROS production is also attenuated by complex II inhibitors that bind either to the dicarboxylate site or the Qp site if succinate is the prevalent substrate [15,16,19,20,24].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [19]
This mechanism is supported by several studies with isolated mitochondria.
“Such a mechanism is supported by several studies with isolated mitochondria [15,16,19,20,24].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [19]
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Bortolami, S., Comelato, E., Zoccarato, F., Alexandre, A., & Cavallini, L. (2008) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-008-9126-1 · Cited by 13 · see citing works
- 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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