Does mtDNA nucleoid organization impact aging?
Does mtDNA nucleoid organization impact aging?
复制标题
DOI：
10.1016/j.exger.2009.12.002
复制
发表时间：
2010-07-01
影响因子：
3.9
通讯作者：
Bogenhagen, Daniel F.
中科院分区：
文献类型：
--
作者：
Bogenhagen, Daniel F.
体细胞在组织培养包装线粒体DNA （mtDNA）的几个拷贝在聚集体被称为类核，似乎是非常稳定的。多个mtDNA基因组聚集在一个单一的类核复合体中，可能会促进许多体细胞组织中mtDNA缺失和点突变的进行性年龄相关积累，特别是在有丝分裂后细胞中。相比之下，卵母细胞似乎有能力选择mtDNA的有害突变，至少在小鼠中是这样。这一根本差异表明，卵母细胞可能比体细胞更能检测和去除有缺陷的mtDNA基因组，部分原因可能是mtDNA在较小的类核中组织更简单。这些观察结果表明，包含多个mtDNA分子的复杂类核结构可能会损害细胞选择有害mtDNA突变的能力，从而导致与年龄相关的线粒体功能障碍。(C) 2009爱思唯尔公司版权所有。
Somatic cells in tissue culture package several copies of mitochondrial DNA (mtDNA) in aggregates known as nucleoids that appear to be remarkably stable. The clustering of multiple mtDNA genomes in a single nucleoid complex may promote the progressive age-related accumulation of deletion and point mutations in mtDNA in many somatic tissues, particularly in post-mitotic cells. In contrast, oocytes appear to have the ability to select against deleterious mutations in mtDNA, at least in mice. This fundamental difference suggests that oocytes may be better able to detect and remove defective mtDNA genomes than somatic cells, possibly due in part to the simpler organization of the mtDNA in smaller nucleoids. These observations suggest the hypothesis that a complex nucleoid structure containing several mtDNA molecules may impair the ability of the cell to select against deleterious mtDNA mutations, thereby contributing to age-related mitochondrial dysfunction. (C) 2009 Elsevier Inc. All rights reserved.