title: The allosteric ATP-inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP-dependent phosphorylation.
abstract: 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 we 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 Deltap low, and the efficiency of energy transduction high. After Ca(2+)-induced dephosphorylation this control is lost, accompanied by increase of Deltap, 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.
authors.affiliation: Fachbereich Chemie, Philipps-Universität, D-35032, Marburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bender
authors.forename: B
authors.initials: B
authors.lastname: Kadenbach
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D003576:Electron Transport Complex IV; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium