Mitochondrial Proton Conductance, Standard Metabolic Rate and Metabolic Depression

Abstract

Proton cycling across the mitochondrial inner membrane makes up a significant proportion (20–30%) of Standard Metabolic Rate (SMR) in rats. If proton cycling is equally important in other animals, those that metabolically depress to 25% or less of SMR have a problem: either their entire energy budget will be wasted by proton cycling, or they have to suppress the leak of protons across the mitochondrial membrane. Muscle mitochondria from metabolically depressed, hypoxic overwintering frogs (Rana temporaria) do have decreased proton leak rate. This is achieved not by decreasing the proton conductance of the membrane, but by lowering the protonmotive force (the driving force for the leak). Protonmotive force is lowered aerobically by restricting electron supply, and in anoxia by restricting mitochondrial ATPase activity. There is also a temperature component to the physiological depression of overwintering frogs. The proton conductance of frog muscle mitochondria decreases steeply with temperature. Frog hepatocytes also respond strongly to temperature, and decrease their proton cycling in parallel to other reactions, so preserving metabolic efficiency at different temperatures. Hepatopancreas cells from the land snail (Helix aspersa) provide a good new model system to study biochemical mechanisms of depression without the complications of temperature change. Cells from aestivating animals show a persistent metabolic depression to 30% of controls, partly through intrinsic effects and partly through the extrinsic effects of pH and pO₂. In depressed cells, proton cycling decreases at least as much as cellular respiration rate. These results using frogs and snails show that mitochondrial proton cycling is strongly suppressed in metabolic depression, so that metabolic efficiency is maintained or even enhanced.