Proton pumping by cytochrome c oxidase - A 40 year anniversary

Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):692-698. doi: 10.1016/j.bbabio.2018.03.009. Epub 2018 Mar 19.


Cytochrome c oxidase is a remarkable energy transducer that seems to work almost purely by Coulombic principles without the need for significant protein conformational changes. In recent years it has become possible to follow key partial reactions of the catalytic cycle in real time, both with respect to electron and proton movements. These experiments have largely set the stage for the proton pump mechanism. The structures of the catalytic binuclear heme‑copper site that is common to the huge family of heme‑copper oxidases, are today well understood throughout the catalytic cycle of oxygen reduction to water based on both spectroscopic studies and quantum chemical calculations. Here, we briefly review this progress, and add some recent details into how the proton pump mechanism is protected from failure by leakage.

Publication types

  • Review

MeSH terms

  • Animals
  • Biochemical Phenomena
  • Catalytic Domain
  • Electron Transport Complex IV / chemistry
  • Electron Transport Complex IV / metabolism*
  • Heme / metabolism*
  • Humans
  • Models, Molecular
  • Proton Pumps / chemistry
  • Proton Pumps / metabolism*


  • Proton Pumps
  • Heme
  • Electron Transport Complex IV