Cytochrome c oxidase and nitric oxide in action: Molecular mechanisms and pathophysiological implications

► Nitric oxide reacts with the metals of the binuclear site of cytochrome c oxidase which is inhibited. ► A nitrosyl-derivative (CcOX-NO) or a nitrite-derivative (CcOX-NO2−) can be formed. ► Persistence of inhibition depends on the prevailing mechanism of reaction. ► Substrates availability, O2 and cytochrome c2+, and the NO concentration control the mechanism. ► Inhibition is O2-competitive only if CcOX nitrosylation occurs.