Cellular Maintenance and Accumulation of Mitochondrial DNA and Its Mutant

已有研究表明，随着年龄的增长，线粒体活性降低，线粒体DNA出现了有限但可检测到的损伤。我们从老年大鼠的几个组织中提取总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体无义突变。以小鼠骨骼肌细胞系C2C12和衰老加速模型(SAM)小鼠为研究对象，建立了线粒体DNA维持和积累的细胞分化和衰老模型。当线粒体蛋白合成抑制剂、四环素和氯霉素抑制肌肉特异性基因和生肌调节基因的表达时，线粒体的生物发生和线粒体DNA的复制在细胞分化和衰老过程中都是无效的。然而，他们的角色还不清楚。提示细胞环境下线粒体应激可引起线粒体DNA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.