Proton Translocation Catalyzed by Mitochondrial Cytochrome Oxidase

Abstract

The chemiosmotic theory of oxidative phosphorylation (Mitchell, 1966) is generally accepted today. According to the theory, the flux of reducing equivalents in the respiratory chain is linked to electrogenic translocation of protons out across the inner mitochondrial membrane, with development of an electrochemical proton gradient (“protonmotive force”) as the primary form of conserved redox energy. The energy is secondarily transduced into the chemical energy of ATP by influx of H⁺ driven by the transmembrane H⁺ gradient and catalyzed by H⁺-ATPase of the mitochondrial membrane. While these general principles of the chemiosmotic theory are agreed upon, there is still considerable controversy as to the mechanism and even the principle of respiration-linked proton translocation. Mitchell’s original suggestion (see Mitchell, 1966) is that the respiratory chain achieves H⁺ translocation by being organized in so-called loops, in which system the terminal segment of the chain, viz. cytochrome c oxidase, would simply function as a transmembrane electron translocator. However, as shown by Wikström and collaborators (Wikström, 1977; Wikström and Saari, 1977; Krab and Wikström, 1978), cytochrome c oxidase functions as a redox-linked proton pump, catalyzing uptake of 2H⁺ from the inside of the mitochondria and release of 1H⁺ to the outside, per electron traversing the span between cytochrome c and molecular oxygen.