Mitochondria Are the Main Cellular Source of O2−, H2O2 and Oxidative Stress
Mitochondria reduce about 1–2 % of the O2 consumed in the tissues to O2− that is dismutated in the mitochondrial matrix by the Mn-SOD reaction to O2 and H2O2. O2− as a charged and non permeable species is confined into the mitochondrial matrix where is kept at a steady state level of 10−10 M. After dismutation, non charged H2O2 freely diffuses to the cytosol, where it is kept at about 10−7 M by catalase and glutathione peroxidase. In the cytosol H2O2 encounters Fe2+ (and Cu+), suffers homolysis by the Fenton/Haber-Weiss reaction, and produces the highly reactive HO•. This radical immediately abstracts one hydrogen atom from unsaturated fatty acids and starts the process of lipoperoxidation, in an open and non-equilibrium situation as long there are unsaturated fatty acids and O2. The free-radical mediated oxidations of phospholipids, proteins and nucleic acids are a consequence of aerobic life. Increased oxidations define the oxidative stress situation. Then, mitochondria are the main cellular source of O2−, of H2O2 and of oxidative stress in the cell. The cellular metabolisms of O2−, H2O2, NO and ONOO− are integrated and faster rates of free-radical mediated reactions are considered the molecular mechanisms of pathological processes and of aging.
KeywordsSuperoxide radical Hydrogen peroxide Hydroxyl radical Oxidative stress Haber-Weiss reaction Steady states Pathology molecular mechanisms Aging
The authors acknowledge to Mg. Rosario Mussaco Sebio and to Mg. Christian Saporito Magriña for their successful experimental work that produced four publications on the toxicity of Fe and Cu overloads.
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