Mitochondrial DNA mutations in human colonic crypt stem cells
Mitochondrial DNA mutations in human colonic crypt stem cells
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DOI：
10.1172/jci200319435
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发表时间：
2003-11-01
影响因子：
15.9
通讯作者：
Turnbull, DM
中科院分区：
文献类型：
--
作者：
Taylor, RW;Barron, MJ;Turnbull, DM
线粒体基因组编码呼吸链的13个基本亚基，具有显着的基于单亲遗传的遗传学。在人类群体中，线粒体基因组具有很高的序列差异率，具有多种多态变异，因此在研究我们物种的进化史方面发挥了重要作用。近年来，致病线粒体DNA(MtDNA)突变在神经系统和其他疾病中的作用也越来越明显。患者有许多不同的线粒体DNA突变，其中一些是线粒体DNA突变，一些是遗传的，但另一些似乎是零星的。也有研究表明，线粒体DNA突变在衰老和癌症中发挥了作用，但在这些疾病中起致病作用的证据还不太清楚。然而，积累的数据表明，线粒体DNA突变经常发生。在这篇文章中，我们描述了一种新的现象：人结肠隐窝干细胞中mtDNA突变的积累，导致其后代出现显着的生化缺陷。这些研究不仅对了解衰老组织和肿瘤中mtDNA突变的发现有重要意义，而且对确定细胞内mtDNA突变的频率也有重要意义。
The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.