摘要
Mitochondria are the only organelles, along with the nucleus, that have their own DNA. Mitochondrial DNA (mtDNA) is a double-stranded circular molecule of ~16.5 kbp that can exist in multiple copies within the organelle. Both strands are translated and encode for 22 tRNAs, 2 rRNAs, and 13 proteins. mtDNA molecules are anchored to the inner mitochondrial membrane and, in association with proteins, form a structure called nucleoid, which exerts a structural and protective function. Indeed, mitochondria have evolved mechanisms necessary to protect their DNA from chemical and physical lesions such as DNA repair pathways similar to those present in the nucleus. However, there are mitochondria-specific mechanisms such as rapid mtDNA turnover, fission, fusion, and mitophagy. Nevertheless, mtDNA mutations may be abundant in somatic tissue due mainly to the proximity of the mtDNA to the oxidative phosphorylation (OXPHOS) system and, consequently, to the reactive oxygen species (ROS) formed during ATP production. In this review, we summarise the most common types of mtDNA lesions and mitochondria repair mechanisms. The second part of the review focuses on the physiological role of mtDNA damage in ageing and the effect of mtDNA mutations in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Considering the central role of mitochondria in maintaining cellular homeostasis, the analysis of mitochondrial function is a central point for developing personalised medicine.
摘要译文
线粒体是唯一具有其DNA的细胞器。线粒体DNA（mtDNA）是一个〜16.5 kbp的双链圆形分子，可以在细胞器中的多个副本中存在。两条链都经过翻译并编码为22个TRNA，2个RRNA和13个蛋白质。 mtDNA分子锚定在线粒体内膜上，并与蛋白质结合形成一种称为核苷的结构，该结构具有结构和保护功能。实际上，线粒体已经发展了保护其DNA免受化学和物理病变（例如DNA修复途径）类似于核中存在的物理病变所必需的机制。然而，存在线粒体特异性机制，例如快速mtDNA的离职，裂变，融合和线粒体。然而，MTDNA突变在体细胞组织中可能很丰富，这主要是由于mtDNA与氧化磷酸化（OXPHOS）系统的接近，因此，与ATP生产过程中形成的反应性氧（ROS）。在这篇综述中，我们总结了mtDNA病变的最常见类型和线粒体修复机制。综述的第二部分重点是mtDNA损伤在衰老中的生理作用以及mtDNA突变在阿尔茨海默氏病和帕金森氏病等神经退行性疾病中的影响。考虑到线粒体在维持细胞稳态中的核心作用，线粒体功能的分析是开发个性化医学的核心。
Veronica Bazzani;Mara Equisoain Redin;Joshua McHale;Lorena Perrone;Carlo Vascotto. Mitochondrial DNA Repair in Neurodegenerative Diseases and Ageing[J]. International Journal of Molecular Sciences, 2022,23(19): 11391