Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions
Mitochondrial production of superoxide and hydrogen peroxide is potentially important in cell signaling and disease. Eleven distinct mitochondrial sites that differ markedly in capacity are known to leak electrons to oxygen to produce O 2 . and/or H 2 O 2 . We discuss their contributions to O 2 . /H 2 O 2 production under native conditions in mitochondria oxidizing different substrates and in conditions mimicking physical exercise and the changes in their capacities after caloric restriction. We review the use of S1QELs and S3QELs, suppressors of mitochondrial O 2 . /H 2 O 2 generation that do not inhibit oxidative phosphorylation, as tools to characterize the contributions of specific sites in situ and in vivo. Superoxide (O 2 . ) 2 and hydrogen peroxide (H 2 O 2 ) are produced by leaks of electrons from donor redox centers of the mitochondrial electron transport chain and associated metabolic enzymes to cause either one-electron or two-electron reduction of oxygen (1, 2). To date, at least 11 sites that produce O 2 . and/or H 2 O 2 (O 2 . /H 2 O 2 ), namely sites O F , B F , A F , P F , I F , I Q ,