mtDNA Rearrangements in Human Development and Disease

线粒体在真核细胞的细胞器中是不寻常的，因为它们拥有自己的细胞器。 基因组，线粒体DNA。线粒体DNA的复制和转录以及线粒体DNA的翻译 编码的蛋白质是氧化磷酸化产生三磷酸腺苷的关键。进化论 对人线粒体DNA的分析和分子研究表明，人线粒体DNA发生了重组。 线粒体DNA的重组在健康个体中发生在低水平，并导致 线粒体DNA重排，其水平随着年龄的增长而增加。在高水平上，线粒体DNA重排可以 导致线粒体功能障碍和人类疾病。很难观察到mtdna重组。 在细胞实验中，由于缺乏合适的mtDNA标记来检测重组。一个 这里描述了使用唯一标记的人类mtDNA的模型系统，其允许检测 分子间和分子内重组mtDNA。这一分析系统将用于确定 线粒体DNA重组产物并测定其形成率。随后， 重组线粒体DNA在细胞中形成的机制将被研究。这些调查 很可能导致对致病线粒体DNA形成机制的重大洞察 重组以及涉及线粒体DNA(包括线粒体DNA)的基本细胞过程 维护、复制和修复机制。

Mitochondria are unusual among the organelles of a eukaryotic cell in that they possess their own genome, the mtDNA. The replication and transcription of mtDNA and the translation of the mtDNA- encoded proteins is essential for the production of ATP by oxidative phosphorylation. Evolutionary analyses and molecular studies of human mtDNA indicate that recombination of human mtDNA occurs. Recombination of mtDNA occurs at low levels in healthy individuals and results in the accumulation of mtDNA rearrangements, whose levels increase with age. At high levels, mtDNA rearrangements can result in mitochondrial dysfunction and human disease. It is difficult to observe mtDNA recombination experimentally in cells because of the lack of appropriate mtDNA markers to detect recombination. A model system is described here that uses uniquely marked human mtDNAs that permit the detection of inter-molecular and intra-molecular recombinant mtDNAs. This system of analysis will be used to identify the products of mtDNA recombination and to determine their rates of formation. Subsequently, the mechanisms by which recombinant mtDNAs are formed in cells will be investigated. These investigations are likely to lead to significant,insights into the mechanism for formation of pathogenic mtDNA rearrangements, as well as into fundamental cellular processes involving mtDNA including mtDNA maintenance, replication, and repair mechanisms.