Physiological diversity of mitochondrial oxidative phosphorylation

1 INSERM, U688 Physiopathologie Mitochondriale, Université Victor Segalen-Bordeaux 2, Bordeaux, France; and 2 IFR 31, Institut Louis Bugnard, BP 84225, UMR 5018 CNRS UPS, Toulouse, France Submitted 20 April 2006 ; accepted in final form 7 June 2006 To investigate the physiological diversity in the regulation and control of mitochondrial oxidative phosphorylation, we determined the composition and functional features of the respiratory chain in muscle, heart, liver, kidney, and brain. First, we observed important variations in mitochondrial content and infrastructure via electron micrographs of the different tissue sections. Analyses of respiratory chain enzyme content by Western blot also showed large differences between tissues, in good correlation with the expression level of mitochondrial transcription factor A and the activity of citrate synthase. On the isolated mitochondria, we observed a conserved molar ratio between the respiratory chain complexes and a variable stoichiometry for coenzyme Q and cytochrome c , with typical values of [1–1.5]:[30–135]:[3]:[9–35]:[6.5–7.5] for complex II:coenzyme Q:complex III:cytochrome c :complex IV in the different tissues. The functional analysis revealed important differences in maximal velocities of respiratory chain complexes, with higher values in heart. However, calculation of the catalytic constants showed that brain contained the more active enzyme complexes. Hence, our study demonstrates that, in tissues, oxidative phosphorylation capacity is highly variable and diverse, as determined by different combinations of 1 ) the mitochondrial content, 2 ) the amount of respiratory chain complexes, and 3 ) their intrinsic activity. In all tissues, there was a large excess of enzyme capacity and intermediate substrate concentration, compared with what is required for state 3 respiration. To conclude, we submitted our data to a principal component analysis that revealed three groups of tissues: muscle and heart, brain, and liver and kidney. respiratory chain; tissues; stoichiometry; cytochrome c ; coenzyme Q Address for reprint requests and other correspondence: R. Rossignol, INSERM U688, Physiopathologie mitochondriale, Université Victor Segalen-Bordeaux 2, 146 rue Léo-Saignat, F-33076 Bordeaux Cedex, France (e-mail: rossig{at}u-bordeaux2.fr )