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 tightly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequence on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper- and hypothyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol intoxication) we found that the increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O(2)/min/mg dry cells) was tightly correlated with total mitochondrial cytochrome content, expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxidase; 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 respiratory chain. Since cytochrome oxidase is well recognized for slippage between redox reactions and proton pumping, we suggest that this dramatic increase in cytochrome oxidase is responsible for the decrease in the overall efficiency of respiratory chain and, in turn, of ATP synthesis yield, linked to the adaptive increase in oxidative phosphorylation capacity.
Nogueira
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Laboratoire de Bioénergétique Fondamentale et Appliquée, Université Joseph Fourier, 38041 Grenoble Cedex, France.
Rigoulet
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Devin
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D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D003580:Cytochromes / Q000378:metabolism; D004579:Electron Transport; D004734:Energy Metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D003580:Cytochromes; D000255:Adenosine Triphosphate; D010100:Oxygen