The sites and topology of mitochondrial superoxide production
- PMID: 20064600
- PMCID: PMC2879443
- DOI: 10.1016/j.exger.2010.01.003
The sites and topology of mitochondrial superoxide production
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.
Copyright (c) 2010 Elsevier Inc. All rights reserved.
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References
-
- Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. 2005;70:200–214. - PubMed
-
- Aon MA, Cortassa S, Marban E, O'Rourke B. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J. Biol. Chem. 2003;278:44735–44744. - PubMed
-
- Babior BM, Lambeth JD, Nauseef W. The neutrophil NADPH oxidase. Arch. Biochem. Biophys. 2002;397:342–344. - PubMed
-
- Barja G. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg. Biomembr. 1999;31:347–366. - PubMed
-
- Barja G. The quantitative measurement of H2O2 generation in isolated mitochondria. J Bioenerg. Biomembr. 2002;34:227–233. - PubMed
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