INTERACTIONS BETWEEN BIOENERGETICS AND MITOCHONDRIAL BIOGENESIS

We studied the interaction between energy metabolism and mitochondrial biogenesis during myogenesis in C2C12 myoblasts. Metabolic rate was n early constant throughout differentiation, although there was a shift in the relative importance of glycolytic and oxidative metabolism, acc ompanied by increases in pyruvate dehydrogenase activation state and t otal activity. These changes in mitochondrial bioenergetic parameters observed during differentiation occurred in the absence of a hypermeta bolic stress. A chronic (3 day) energetic stress was imposed on differ entiated myotubes using sodium azide to inhibit oxidative metabolism. When used at low concentrations, azide inhibited more than 70% of cyto chrome oxidase (COX) activity without changes in bioenergetics (either lactate production or creatine phosphorylation) or mRNA for mitochond rial enzymes. Higher azide concentrations resulted in changes in bioen ergetic parameters and increases in steady state COX II mRNA levels. A zide did not affect mtDNA copy number or mRNA levels for other mitocho ndrial transcripts, suggesting azide affects stability, rather than sy nthesis, of COX II mRNA. These results indicate that changes in bioene rgetics can alter mitochondrial genetic regulation, but that mitochond rial biogenesis accompanying differentiation occurs in the absence of hypermetabolic challenge. (C) 1998 Elsevier Science B.V. All rights re served.