Factors Modulating the Oxygen Dependence of Mitochondrial Oxidative Phosphorylation

Abstract

The oxygen consumed by mitochondrial oxidative phosphorylation is reduced to water by the enzyme cytochrome c oxidase. This reaction has the overall stoichiometry:

$$4{H^{ + \;}} + \;{0_{2\;}} + \;4{c^{2 + \;}} + \;2ADP\; + \;2Pi\, \to \,4{c^{3 + }} + \;{H_2}0\; + \;2ATP $$

((1))

Electrons from cytochrome c and hydrogen ions from the aqueous phase are required for reduction of dioxygen to water. In order to understand the role of cytochrome c oxidase in the regulation of mitochondrial respiration, one must keep in mind that the reduction of dioxygen to water is irreversible under all metabolic conditions. This means that in any steady state the rate of respiration is equal to the rate of electron transfer through cytochrome £ oxidase. In order for the mitochondrial respiratory rate to change it is necessary for the rate of oxygen reduction by cytochrome £ oxidase to change by the same amount and in the same direction. Metabolic effectors of the rate of mitochondrial respiration in vivo and in vitro ultimately do so by modulating the rate of electron transfer through cytochrome £ oxidase. Part of the energy available in the cytochrome c oxidase reaction is released as heat and part is conserved by the synthesis of ATP. The latter occurs through a coupling mechanism which involves reaction intermediates, i.e., there is no direct interaction of ADP, Pi or ATP with the enzyme.

Supported by grant GM-21524 from the National Institutes of Health.