Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
Biochem J. 2021 Mar 26;478(6):1179-1197. doi: 10.1042/BCJ20200920.
Mitochondria are semiautonomous organelles in eukaryotic cells and possess their own genome that replicates independently. Mitochondria play a major role in oxidative phosphorylation due to which its genome is frequently exposed to oxidative stress. Factors including ionizing radiation, radiomimetic drugs and replication fork stalling can also result in different types of mutations in mitochondrial DNA (mtDNA) leading to genome fragility. Mitochondria from myopathies, dystonia, cancer patient samples show frequent mtDNA mutations such as point mutations, insertions and large-scale deletions that could account for mitochondria-associated disease pathogenesis. The mechanism by which such mutations arise following exposure to various DNA-damaging agents is not well understood. One of the well-studied repair pathways in mitochondria is base excision repair. Other repair pathways such as mismatch repair, homologous recombination and microhomology-mediated end joining have also been reported. Interestingly, nucleotide excision repair and classical nonhomologous DNA end joining are not detected in mitochondria. In this review, we summarize the potential causes of mitochondrial genome fragility, their implications as well as various DNA repair pathways that operate in mitochondria.
线粒体是真核细胞中的半自主细胞器，拥有独立复制的自身基因组。由于在线粒体中进行氧化磷酸化，线粒体基因组经常受到氧化应激的影响。电离辐射、类放射药物和复制叉停滞等因素也会导致线粒体 DNA（mtDNA）发生不同类型的突变，从而导致基因组脆弱性。来自肌肉疾病、运动障碍和癌症患者样本的线粒体显示出频繁的 mtDNA 突变，如点突变、插入和大规模缺失，这些突变可能与与线粒体相关的疾病发病机制有关。暴露于各种 DNA 损伤剂后，这些突变是如何产生的机制尚不清楚。线粒体中研究得很好的修复途径之一是碱基切除修复。其他修复途径，如错配修复、同源重组和微同源介导的末端连接，也有报道。有趣的是，核苷酸切除修复和经典的非同源 DNA 末端连接在线粒体中未被检测到。在这篇综述中，我们总结了线粒体基因组脆弱性的潜在原因、它们的影响以及在线粒体中起作用的各种 DNA 修复途径。
