The assumption that nitric oxide inhibits mitochondrial ATP synthesis is correct

Abstract

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.