The assumption that nitric oxide inhibits mitochondrial ATP synthesis is correct

The assumption that reversible inhibition of mitochondrial respiration by nitric oxide (NO.) represents inhibition of ATP synthesis is unproven. NO. could theoretically inhibit the oxygen consumption with continued ATP synthesis, by acting as an electron acceptor from cytochrome c or as a terminal electron acceptor in stead of oxygen, We report here that NO. does reversibly inhibit brain mitochondrial ATP synthesis with a time course similar to its inhibition of respiration. Whilst such inhibition was largely reversible, there appeared to be a small irreversible component which may theoretically be due to peroxynitrite formation, i.e, as a result of the reaction between NO. and superoxide, generated by the mitochondrial respiratory chain. (C) 1999 Federation of European Biochemical Societies.