The allosteric ATP-inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP-dependent phosphorylation

In previous studies the allosteric inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP-ratios via binding of the nucleotides to the matrix domain of subunit IV was demonstrated. Here me show that the allosteric ATP-inhibition of the isolated bovine heart enzyme is switched on by cAMP-dependent phosphorylation with protein kinase A of subunits II (and/or III) and Vb, and switched off by subsequent incubation with protein phosphatase 1. It is suggested that after cAMP-dependent phosphorylation of cytochrome c oxidase mitochondrial respiration is controlled by the ATP/ADP-ratio keeping the proton motive force Delta p low, and the efficiency of energy transduction high. After Ca2+-induced dephosphorylation this control is lost, accompanied by increase of Delta p, slip of proton pumping (decreased H(+/)e(-) stoichiometry), and increase of the rate of respiration and ATP-synthesis at a decreased efficiency of energy transduction. (C) 2000 Federation of European Biochemical Societies.