Cell respiration is controlled by ATP, an allosteric inhibitor of cytochrome-c oxidase

Eur J Biochem. 1997 Oct 1;249(1):350-4. doi: 10.1111/j.1432-1033.1997.t01-1-00350.x.


The activity of cytochrome-c oxidase, the terminal enzyme of the mitochondrial respiratory chain, is known to be regulated by the substrate pressure, i.e. the ferro-/ferricytochrome c ratio, by the oxygen concentration, and by the electrochemical proton gradient delta muH+ across the inner mitochondrial membrane. Here we describe a further mechanism of 'respiratory control' via allosteric inhibition of cytochrome-c oxidase by ATP, which binds to the matrix domain, of subunit IV. The cooperativity between cytochrome-c-binding sites in the dimeric enzyme complex is mediated by cardiolipin, which is essential for cooperativity of the enzyme within the lipid membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphate / metabolism*
  • Allosteric Regulation
  • Animals
  • Binding Sites
  • Cardiolipins / metabolism
  • Cell Respiration / physiology*
  • Dimerization
  • Electron Transport Complex IV / antagonists & inhibitors*
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / metabolism
  • Enzyme Inhibitors / metabolism
  • In Vitro Techniques
  • Kinetics
  • Membrane Lipids / metabolism
  • Mitochondria, Heart / metabolism
  • Protein Conformation
  • Tuna / metabolism


  • Cardiolipins
  • Enzyme Inhibitors
  • Membrane Lipids
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Electron Transport Complex IV