Control of mitochondrial membrane potential and ROS formation by reversible phosphorylation of cytochrome c oxidase.
Phosphorylation of isolated cytochrome c oxidase from bovine kidney and heart, and of the reconstituted heart enzyme, with protein kinase A, cAMP and ATP turns on the allosteric ATP-inhibition at high ATP/ADP ratios. Also incubation of isolated bovine liver mitochondria only with cAMP andATP turns on, and subsequent incubation with Ca2+ turns off the allosteric ATP-inhibition of cytochrome c oxidase. In the bovine heart enzyme occur only three consensus sequences for cAMP-dependent phosphorylation (in subunits I, III and Vb). The evolutionary conservation of RRYS441 at the cytosolic side of subunit I, together with the above results, suggest that phosphorylation of Ser441 turns on the allosteric ATP-inhibition of cytochrome c oxidase. The results support the 'molecular-physiological hypothesis' [29], which proposes a low mitochondrial membrane potential through the allosteric ATP-inhibition. A hormone- or agonist-stimulated increase of cellular [Ca2+] is suggested to activate a mitochondrial protein phosphatase which dephosphorylates cytochrome c oxidase, turns off the allosteric ATP-inhibition and results in increase of mitochondrial membrane potential and ROS formation.
Lee
Icksoo
I
Fachereich Chemie, Philipps-University, Marburg, Germany.
Bender
Elisabeth
E
Kadenbach
Bernhard
B
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008564:Membrane Potentials; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D017382:Reactive Oxygen Species; D003576:Electron Transport Complex IV