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、转录和翻译- 编码的蛋白质是通过氧化磷酸化产生ATP所必需的。进化 对人mtDNA的分析和分子研究表明，人mtDNA发生重组。 线粒体DNA的降解在健康个体中以低水平发生，并导致线粒体DNA的积累。 线粒体DNA重排，其水平随年龄增长而增加。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。观察mtDNA重组是困难的 由于缺乏合适的mtDNA标记来检测重组，因此在细胞中进行实验。一 这里描述了一个模型系统，它使用独特标记的人类mtDNA，允许检测 分子间和分子内重组mtDNA。该分析系统将用于识别 线粒体DNA重组的产物，并确定其形成率。随后 将研究重组mtDNA在细胞中形成的机制。这些调查 可能会导致对致病性mtDNA形成机制的重要见解 重组，以及涉及mtDNA的基本细胞过程，包括mtDNA 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.