INHIBITION OF MITOCHONDRIAL PROTEIN-SYNTHESIS IMPAIRED C2C12 MYOBLASTDIFFERENTIATION

Various factors are required for the regulation of muscle cell differe ntiation. In an attempt to elucidate the mechanism underlying myogenes is, we examined the possible contribution of mitochondria to terminal differentiation of murine myoblast cell line, C2C12, using a specific inhibitor for mitochondrial protein synthesis, tetracycline. Tetracycl ine impaired myotube formation and induction of muscle creatine kinase activity which was specifically observed in differentiated myocytes. Transcript levels of muscle-specific proteins, creatine kinase and tro ponin-I were also significantly suppressed in a dose-dependent manner. However, those proteins with myogenic regulatory factors, MyoD and my ogenin, and common proteins including glycolytic enzymes were not affe cted. Cellular viability, mitochondrial transcription, and mitochondri al proliferation were confirmed not to be impaired by tetracycline tre atment. These results suggest that mitochondrial stress may affect reg ulation of differentiation-specific gene expression. This system may c ontribute to an understanding of mechanisms for differentiation inhibi tion caused by inhibitors of mitochondrial protein synthesis that have also been observed in other kinds of cells.