The sites and topology of mitochondrial superoxide production

Brand, Martin D.

doi:10.1016/j.exger.2010.01.003

Cited by 1,217Mitochondrial Function and PathologyRedox biology and oxidative stressCoenzyme Q10 studies and effects

The sites and topology of mitochondrial superoxide production

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Brand, Martin D.·2010·Experimental Gerontology

DOI 10.1016/j.exger.2010.01.003PMC PMC2879443

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Abstract

Mitochondrial superoxide production is an important source of reactive oxygen species in cells, and may cause or contribute to ageing and the diseases of ageing. Seven major sites of superoxide production in mammalian mitochondria are known and widely accepted. In descending order of maximum capacity they are the ubiquinone-binding sites in complex I (site IQ) and complex III (site IIIQo), glycerol 3-phosphate dehydrogenase, the flavin in complex I (site IF), the electron transferring flavoprotein:Q oxidoreductase (ETFQOR) of fatty acid beta-oxidation, and pyruvate and 2-oxoglutarate dehydrogenases. None of these sites is fully characterized and for some we only have sketchy information. The topology of the sites is important because it determines whether or not a site will produce superoxide in the mitochondrial matrix and be able to damage mitochondrial DNA. All sites produce superoxide in the matrix; site IIIQo and glycerol 3-phosphate dehydrogenase also produce superoxide to the intermembrane space. The relative contribution of each site to mitochondrial reactive oxygen species generation in the absence of electron transport inhibitors is unknown in isolated mitochondria, in cells or in vivo, and may vary considerably with species, tissue, substrate, energy demand and oxygen tension.

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Mitochondria-derived ROS are mainly produced by complexes I and III as O2−.
“Mitochondria-derived ROS (mtROS) are mainly produced by complexes I and III as O2●−.”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [85]
The Nox enzyme family and the respiratory electron transport chain of mitochondria are the two major sources of ROS in many eukaryotic cells.
“The enzyme family of NADPH oxidases (Nox) [13,83] and the respiratory electron transport chain (ETC) of mitochondria [84,85,86] are the two major sources of ROS in many eukaryotic cells.”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [85]
Complex I produces O2− into the mitochondrial matrix where it is dismutated by SOD2 to H2O2.
“Complex I produces O2●− into the mitochondrial matrix where it is dismutated by SOD2 to H2O2 [67,84,85,86].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [85]

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Authors: Brand, M. D.
Affiliations: Buck Institute for Research on Aging (US)
Corresponding author: Brand, Martin D.
ORCID: Brand, Martin D.
Venue: Experimental Gerontology
Publisher: Elsevier BV
Published: 2010-08
Volume: 45
Issue: 7-8
Pages: 466-472
ISSN: 0531-5565 (ISSN-L)
DOI: 10.1016/j.exger.2010.01.003
PMC: PMC2879443
OpenAlex: W2056015556
Cited by: 1,217
References: 115
Citations by year: 2026: 74 · 2025: 71 · 2024: 51 · 2023: 65 · 2022: 85 · 2021: 129 · 2020: 93 · 2019: 74 · 2018: 78 · 2017: 63 · 2016: 91 · 2015: 63 · 2014: 85 · 2013: 66 · 2012: 67
FWCI: 25.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Experimental Gerontology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: W. M. Keck Foundation
National Institutes of Health (P01 AG025901, PL1 AG032118, R01 AG033542, P30 AG025708)
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: mitochondrial superoxide production, reactive oxygen species, mitochondrial complex I, cytochrome bc1 complex, glycerol-3-phosphate dehydrogenase, electron transfer flavoprotein, pyruvate dehydrogenase, 2-oxoglutarate dehydrogenase, mitochondrial DNA damage, mitochondrial matrix, intermembrane space, aging, electron transport chain
MeSH terms: Aging, Animals, Binding Sites, Free Radicals, Humans, Mitochondria, Models, Biological, Superoxides, Electron Transport Complex III, Reactive Oxygen Species, Electron Transport Complex I

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The sites and topology of mitochondrial superoxide production

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