Experimental Discrimination between Proton Leak across the Mitochondrial Membrane and Slip in the Proton Pumps of the Electron Transport Chain

Abstract

It has been known since 1974 that when mitochondrial State 4 respiration on succinate is titrated with a respiratory inhibitor such as malonate, the relationship between protonmotive force (Δp) and respiration rate (J _o) is non-linear. This has been interpreted in a number of different ways, but there are two current models to explain the non-linearity^1,2. There is either

• (a) a non-ohmic proton leak (an increase in the proton conductance of the inner membrane at high Δp), so that the rate of respiration is disproportionately high at high potential, but the number of protons pumped by the chain per oxygen consumed (the H⁺/O ratio) remains constant, or

• (b) a slip reaction in the electron transport chain, so that electron flow is not always accompanied by proton pumping and the H⁺/O ratio is decreased at higher Δp, leading to a faster respiration rate at high potential to drive a proton leak that depends linearly on potential.