Cellular Maintenance and Accumulation of Mitochondrial DNA and Its Mutant

研究表明，随着年龄的增长，线粒体活性降低，线粒体DNA的损伤程度有限，但可以检测到。从老年大鼠的几种组织中提取总DNA，检测线粒体DNA的核苷酸变化。线粒体具有异质性基因组和许多母系无义突变。作为维持和积累线粒体DNA的细胞分化和衰老模型，我们使用小鼠骨骼肌细胞系C2C12和衰老加速模型（SAM）小鼠。当肌肉特异性基因和生肌调节基因的表达被抑制与线粒体蛋白质合成的抑制剂，四环素和氯霉素，线粒体的生物合成和线粒体DNA的复制是无效的细胞分化和衰老过程中。然而，它们的作用尚不明确。结果表明，细胞内环境对线粒体的胁迫可诱导线粒体DNA的含量和转录水平的变化。

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.