Cellular Maintenance and Accumulation of Mitochondrial DNA and Its Mutant

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It has been shown that mitochondrial activity reduced with age, and limited but detectable damages in mitochondrial DNA were accumulated in aged person. We were examined nucleotide changes of mitochondrial DNA using total DNA extracted from several tissues of old rats. Mitochondria had heterogeneous genomes and many maternal nonsense mutations. As a model of cell differentiation and aging for maintenance and accumulation of mitochondrial DNA,we used a murine skeletal muscle cell line C2C12 and senescence-accelerated model (SAM) mouse. When expression of the muscle-specific genes and myogenic regulatory genes were inhibited with inhibitors of mitochondrial protein synthesis, tetracycline and chloramphenicol, biogenesis of mitochondria and replication of mitochondrial DNA were ineffective during cell differentiation and aging. Their roles, however, are not yet clear. It was suggested that mitochondrial stress suffered from cellular environment induces the content of mitochondrial DNA and the levels of mitochondrial transcription.