Oxygen Activation and Energy Conservation by Cytochrome c Oxidase

Mårten Wikström*, Klaas Krab, Vivek Sharma

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


This review focuses on the type A cytochrome c oxidases (CcO), which are found in all mitochondria and also in several aerobic bacteria. CcO catalyzes the respiratory reduction of dioxygen (O2) to water by an intriguing mechanism, the details of which are fairly well understood today as a result of research for over four decades. Perhaps even more intriguingly, the membrane-bound CcO couples the O2 reduction chemistry to translocation of protons across the membrane, thus contributing to generation of the electrochemical proton gradient that is used to drive the synthesis of ATP as catalyzed by the rotary ATP synthase in the same membrane. After reviewing the structure of the core subunits of CcO, the active site, and the transfer paths of electrons, protons, oxygen, and water, we describe the states of the catalytic cycle and point out the few remaining uncertainties. Finally, we discuss the mechanism of proton translocation and the controversies in that area that still prevail.

Original languageEnglish
Pages (from-to)2469-2490
Number of pages22
JournalChemical Reviews
Issue number5
Early online date19 Jan 2018
Publication statusPublished - 14 Mar 2018


This work was supported by Societas Scientiarum Fennica (MW), the Magnus Ehrnrooth Foundation (MW, VS), and the Academy of Finland (VS). M.W. is grateful to Jonathan P. Hosler, Peter R. Rich, and Denis L. Rousseau for helpful comments and access to unpublished material. V.S. is thankful to the Center for Scientific Computing, Finland, for computational resources.

FundersFunder number
Academy of Finland
Magnus Ehrnroothin Säätiö
Societas pro Fauna et Flora Fennica


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