Reynier P, Malthiery Y
Unité 38 de l'INSERM, Laboratoire de Biochimie médicale, Faculté de Médecine, Marseille, France.
Biochem Biophys Res Commun. 1995 Dec 5;217(1):59-67. doi: 10.1006/bbrc.1995.2745.
Multiple deletions of mtDNA have not only been implicated in aging, but also in a wide variety of pathological conditions. The enzyme system used in long-PCR makes it possible to synthesize the entire mitochondrial genome (16.5 kb), exposing the multiple deletions in mtDNAs implicated in and, at least partially, responsible for these pathologies. But it is not the number or type of anomalous mtDNA that is crucial, rather it is their frequency relative to the number of intact copies of the mitochondrial genome. Our work exposes the necessity of quantitating the number of normal mitochondrial DNAs. The accuracy of the technique and the small sample size required permit one to detect multiple deletions, located in a specific organ, and simultaneously measure the fraction of intact molecules. This fraction can then be correlated with mitochondrial dysfunction to serve both as an indicator of tissue aging and a monitor of an impending myopathy.
线粒体DNA的多重缺失不仅与衰老有关，还与多种病理状况相关。长链聚合酶链式反应（long-PCR）中使用的酶系统能够合成完整的线粒体基因组（16.5 kb），从而揭示出与这些病理状况相关且至少部分导致这些病理状况的线粒体DNA中的多重缺失。但关键的并非异常线粒体DNA的数量或类型，而是它们相对于线粒体基因组完整拷贝数的频率。我们的研究揭示了定量正常线粒体DNA数量的必要性。该技术的准确性以及所需的小样本量使得人们能够检测位于特定器官中的多重缺失，并同时测量完整分子的比例。然后可以将该比例与线粒体功能障碍相关联，既作为组织衰老的指标，又作为即将发生的肌病的监测指标。
