ROS Formation in Mitochondria and Defensive Mechanism

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Mitochondrial ROS are reactive oxygen species (ROS) that are produced by mitochondria. Generation of mitochondrial ROS mainly takes place at the electron transport chain located on the inner mitochondrial membrane during the process of oxidative phosphorylation (OXPHOS). Leakage of electrons at complex I and complex III from electron transport chains leads to partial reduction of oxygen to form superoxide. Subsequently, superoxide is quickly dismutated to hydrogen peroxide by two dismutases including superoxide dismutase 2 (SOD2) in mitochondrial matrix and superoxide dismutase 1 (SOD1) in mitochondrial intermembrane space. Collectively, both superoxide and hydrogen peroxide generated in this process are considered as mitochondrial ROS.[3]

Once thought as merely the by-products of cellular metabolism, mitochondrial ROS are increasingly viewed as important signaling molecules, whose levels of generation at 11 currently-identified sites vary depending on cellular energy supply and demand.[5][6] At low levels, mitochondrial ROS are considered to be important for metabolic adaptation as seen in hypoxia. Mitochondrial ROS, stimulated by danger signals such as lysophosphatidylcholine and Toll-like receptor 4 and Toll-like receptor 2 bacterial ligands lipopolysaccharide (LPS) and lipopeptides, are involved in regulating inflammatory response