The sites and topology of mitochondrial superoxide production

By M. Brand. Experimental Gerontology, 2010

1,146 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/66a31ece45c2a8ffdc79af6355dea7f22ef3d5bd

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Citations in the corpus

Role of ROS and RNS Sources in Physiological and Pathological Conditions (2016, background): “To date, the relative importance of each mitochondrial site to ROS production is still controversial, partly due to utilization of different assays, substrates [36], and sources of mitochondria [37].”
Fundamentals of cancer metabolism (2016, background): “The mitochondria and cytosolic NADPH oxidases (NOXs) produce O2 − from the one-electron reduction of oxygen (115).”
Reperfusion injury and reactive oxygen species: The evolution of a concept (2015, background): “another NAD-linked dehydrogenase that is localized to the outer surface of the inner membrane and capable of generating ROS primarily into the intermembrane space [317,362].”
Calcium and ROS: A mutual interplay (2015, background): “Superoxide can be generated at different sites within the mitochondria [22].”
Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease (2014, background): “Mitochondrial Ca(2) + also activates nitric oxide synthase, whose product disturbs the ETC and enhances ROS generation (16, 159).”
Mitochondrial reactive oxygen species and cancer (2014, background): “The mitochondria have eight known sites that are capable of producing superoxide [16,17].”
Mitochondrial complex III ROS regulate adipocyte differentiation (2011, positive): “Complex III has the ability to generate superoxide within the matrix or intermembrane space (Brand, 2010).”
ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells (2019, neutral): “dehydrogenase, and 2-oxoglutarate dehydrogenase [10].”
ROS Function in Redox Signaling and Oxidative Stress (2014, background): “H2O2 is generated from superoxide produced by mitochondria and NADPH oxidases [8,9].”