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Models Of Mitochondrial Oxidative Stress

E. Cadenas, A. Boveris
Published 2011 · Chemistry

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Mitochondria are sources of H2O2 under aerobic and physiological ­conditions; the mitochondrial H2O2 generation is conceived as a consequence of the univalent and nonenzymatic reduction of oxygen to superoxide anion followed by its disproportionation to H2O2. Recognized sites for the univalent reduction of ­oxygen to superoxide are the autoxidation of ubisemiquinone in complex I and complex III and probably the autoxidation of the flavin semiquinone in complex I. The formation of H2O2 by mitochondria acquires further significance when ­considering that it reports a high mitochondrial energy charge by its diffusion to the cytosol and that it may be involved in domain-specific signaling pathways or ­signaling in localized subcellular areas. H2O2 is considered a major player in the redox regulation of cell signaling by modulating the activity of glutathione-, ­thioredoxin-, and peroxiredoxin-supported systems. Although H2O2 is highly ­diffusible across biological membranes, significant gradients are established in the cells and the involvement of mitochondrial H2O2 in the regulation of specific signaling pathways requires careful consideration of its sources, of its removal by specific enzymic systems, and of the mechanism by which H2O2 modifies the signaling pathways.
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