Control of mitochondrial membrane potential and ROS formation by reversible phosphorylation of cytochrome c oxidase

  • Icksoo Lee
  • Elisabeth Bender
  • Bernhard Kadenbach
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


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 and ATP 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 RRYS441at the cytosolic side of subunit I, together with the above results, suggest that phosphorylation of Ser441turns 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. (Mol Cell Biochem 234/235: 63–70, 2002)

Key words

allosteric ATP-inhibition cAMP-dependent phosphorylation cytochrome c oxidase mechanism of respiratory control mitochondrial membrane potential ROS formation 


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Icksoo Lee
    • 1
  • Elisabeth Bender
    • 1
  • Bernhard Kadenbach
    • 1
  1. 1.Fachbereich ChemiePhilipps-UniversityMarburgGermany

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