Mitochondrial respiratory chain adjustment to cellular energy demand

Because adaptation to physiological changes in cellular energy demand is a crucial imperative for life, mitochondrial oxidative phosphorylation is tig htly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequenc e on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper- and hyp othyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol int oxication) we found that the increase in hepatocyte respiration (from 9.8 t o 22.7 nmol of O-2/min/mg dry cells) was tightly correlated with total mito chondrial cytochrome content, expressed both per mg dry cells or per mg mit ochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxid ase; while total cytochrome content increased 2-fold (from 0.341 +/- 0.021 to 0.821 +/- 0.024 nmol/mg protein), cytochrome oxidase increased 10-fold ( from 0.020 +/- 0.002 to 0.224 +/- 0.006 nmol/mg protein). This modification was associated with a decrease in the overall efficiency of the respirator y chain. Since cytochrome oxidase is well recognized for slippage between r edox reactions and proton pumping, we suggest that this dramatic increase i n cytochrome oxidase is responsible for the decrease in the overall efficie ncy of respiratory chain and, in turn, of ATP synthesis yield, linked to th e adaptive increase in oxidative phosphorylation capacity.