CAUSES OF DIFFERENCES IN RESPIRATION RATE OF HEPATOCYTES FROM MAMMALS OF DIFFERENT BODY-MASS

Resting O-2 consumption of hepatocytes isolated from mammals ranging in mass from 20-g mice to 200-kg horses decreases with increasing body mass. The substrate oxidation system increases in activity with increasing body mass and mitochondrial proton leak and phosphorylation system decrease in activity, resulting in a higher mitochondrial membrane potential in hepatocytes from larger mammals. The absolute rates of O-2 consumption due to nonmitochondrial processes, substrate oxidation, mitochondrial proton leak, and the phosphorylation system decrease with increasing body mass. These decreases are due partly to a decrease in mitochondrial number per cell and partly to decreases in mitochondrial inner membrane proton leakiness and in ATP turnover by cells from larger mammals. Quantitatively, the proportion of total cell O-2 consumption by nonmitochondrial processes (13%) and oxidation of substrates (87%) and the proportions used to drive mitochondrial proton leak (19%) and the phosphorylation system (68%) are the same for hepatocytes from all mammals investigated. The effect of matched decreases in the rates of proton leak and of ATP turnover is to keep the effective amount of ATP synthesized per unit of O-2 consumed relatively constant with body mass, suggesting that the observed value is optimal.