The Mechanism of Uncoupling of Oxidative Phosphorylation

Abstract

Following the pioneer studies of Mitchell and Moyle (1) it is now generally accepted that there exists a correlation between protonophoric effects and uncoupling of oxidative phosphorylation. However conclusive evidence has never been reported that the uncoupling is exclusively due to the increase of membrane conductance for protons. In fact the quantitative comparison carried out by Mitchell and Moyle (1) was based on estimates of Δμ̃_H which were too high and on values of H⁺/e⁻ stoichiometries which were too low than later established. By introducing the correct values of Δμ̃_H and H⁺/e⁻ stoichiometries from the values of membrane conductance and rate of respiration, observed by Mitchell and Moyle (1), it is possible to calculate that the proton efflux via the pump is several times higher than the proton influx via the membrane. Recently our laboratory has provided experimental evidence that the rate of electron transfer multiplied by the H⁺e⁻ stoichiometry is higher than the dissipative proton influx at the same (2). The discrepancy has been attributed to intrinsic uncoupling (slip) of the redox proton pumps whereby electrons can be transferred without proton pumping (3–6).