Cytochrome c oxidase: exciting progress and remaining mysteries

Abstract

Cytochrome c oxidase generates a proton motive force by two separate mechanisms. The first mechanism is similar to that postulated by Peter Mitchell, and is based on electrons and protons used to generate water coming from opposite sides of the membrane. The second mechanism was not initially anticipated, but is now firmly established as a proton pump. A brief review of the current state of our understanding of the proton pump of cytochrome oxidase is presented. We have come a long way since the initial observation of the pump by Mårten Wikström in 1977, but a number of essential questions remain to be answered.

Fig. 1

Several schemes by which redox reactions are coupled to the generation of a transmembrane potential and proton motive force. In each case, the upper side of the membrane is the positive side (P-side or outside), and corresponds to the bacterial periplasm or mitochondrial intermembrane space

Fig. 2

Schematic of subunits I and II of the cytochrome c oxidase from R. sphaeroides, showing the metal centers and two proton-input channels

Fig. 3

Model of cytochrome oxidase from 1978 illustrating the early recognition of the need for proton channels and the positioning of the two hemes. From (Artzatbanov et al. 1978)