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