Mitochondrial cytochrome c oxidase and control of energy metabolism: measurements in suspensions of isolated mitochondria

J Appl Physiol (1985). 2014 Dec 15;117(12):1424-30. doi: 10.1152/japplphysiol.00736.2014. Epub 2014 Oct 16.


Cytochrome c oxidase is the enzyme responsible for oxygen consumption by mitochondrial oxidative phosphorylation and coupling site 3 of oxidative phosphorylation. In this role it determines the cellular rate of ATP synthesis by oxidative phosphorylation and is the key to understanding how energy metabolism is regulated. Four electrons are required for the reduction of oxygen to water, and these are provided by the one-electron donor, cytochrome c. The rate of oxygen consumption (ATP synthesis) is dependent on the fraction of cytochrome c reduced (fred), oxygen pressure (pO2), energy state ([ATP]/[ADP][Pi]), and pH. In coupled mitochondria (high energy state) and pO2 >60 torr, the rate increases in an exponential-like fashion with increasing fred. When the dependence on fred is fitted to the equation rate = A: (fred)(b), A: decreased from 100 to near 20, and B: increased from 1.3 to 4 as the pH of the medium increased from 6.5 to 8.3. During oxygen depletion from the medium fred progressively increases and the rate of respiration decreases. The respiratory rate falls to ½ (P50) by about 1.5 torr, at which point fred is substantially increased. The metabolically relevant dependence on pO2 is obtained by correcting for the increase in fred, in which case the P50 is 12 torr. Adding an uncoupler of oxidative phosphorylation eliminates the dependence of the cytochrome c oxidase activity on pH and energy state. The respiratory rate becomes proportional to fred and the P50 decreases to less than 1 torr.

Keywords: cytochrome oxidase; energy metabolism; hypoxia; oxidative phosphorylation; oxygen; respiratory control.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Respiration
  • Electron Transport Complex IV / metabolism*
  • Energy Metabolism*
  • Homeostasis
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Kinetics
  • Male
  • Mitochondria, Liver / enzymology*
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Oxygen / metabolism*
  • Oxygen Consumption
  • Pressure
  • Rats, Sprague-Dawley


  • Adenosine Triphosphate
  • Electron Transport Complex IV
  • Oxygen