Control of respiration in non-phosphorylating mitochondria is shared between the proton leak and the respiratory chain.

We measured the relationship between rate of respiration and membrane potential in isolated mitochondria titrated with malonate (to inhibit the electron transport chain) or with uncoupler (to increase the proton conductance of the inner membrane). We used the flux control summation and connectivity theorems of metabolic control theory to calculate the control over non-phosphorylating respiration exerted by the respiratory chain (and associated reactions) and by the leak of protons across the inner membrane. At 37 degrees C the flux control coefficient of the leak over respiration was 0.66; the flux control coefficient of the chain over respiration was 0.34. At 25 degrees C the values were 0.75 and 0.25 respectively. We argue that the basis for previous conclusions that all the control is exerted by the proton leak under similar conditions is invalid.