Superoxide production by the mitochondrial respiratory chain.

Most of the oxygen consumed by aerobic organisms is reduced to water by the enzyme cytochrome c oxidase in the terminal reaction of the mitochondrial respiratory chain. Since oxygen in the ground state is in a triplet configuration (with two unpaired electrons in the outer shell) its reduction to water must occur in four consecutive one-electron steps. Some of the partially reduced oxygen intermediates generated in this process are very stable but the enzyme cytochrome c oxidase is able to retain them until all the electrons are transferred. However, a small proportion of the oxygen molecules (1-2% (Boveris et al., 1973)) are converted to superoxide anion radical (Of) by other respiratory components. There are two main sites in the respiratory chain where these reactions occur: Complex I [NADH dehydrogenase, (Turrens et al., 1980)] and Complex III [ubisemiquinone, (Boveris et al., 1976; Cadenas et al., 1977; Turrens et al., 1985)]. Several studies have shown that both sites generate only Of as opposed to a mixture of partially reduced oxygen species, suggesting that the electron donors are either stable radicals or one-electron donors. Hydrogen peroxide is produced as a secondary product (via Of dismutation), and therefore the stoichiometry between Of and H2O2 is close to 2.0 (Cadenas et al., 1977).