Functional mitochondrial heterogeneity in heteroplasmic cells carrying the mitochondrial DNA mutation associated with the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes)
Functional mitochondrial heterogeneity in heteroplasmic cells carrying the mitochondrial DNA mutation associated with the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes)
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DOI：
10.1203/00006450-200008000-00005
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发表时间：
2000-08-01
影响因子：
3.6
通讯作者：
Lombès, A
中科院分区：
文献类型：
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作者：
Bakker, A;Barthélémy, C;Lombès, A
大多数与人类疾病相关的线粒体 DNA (mtDNA) 改变都是异质性的，即突变的 mtDNA 分子与细胞内的正常 mtDNA 分子共存。我们通过对随着 MELAS (A3243G) mtDNA 转移 RNA 点突变比例增加的细胞杂种克隆进行组织学分析，探讨了线粒体间交换的可能性。根据共聚焦和电子显微镜，来自克隆异质细胞群的单个细胞中线粒体DNA依赖性细胞色素c氧化酶活性和蛋白质组成以及线粒体膜电位出现异质性。有缺陷的细胞数量随着突变负荷的增加而增加。我们的结论是，在我们研究的细胞类型中存在异质 mtDNA 突变的情况下，线粒体间分子交换无法提供互补分子（例如野生型 mtDNA、转移 RNA 或蛋白质）的有效均匀分布。因此，这些异质细胞中的线粒体不能被视为单一功能单位。
Most mitochondrial DNA (mtDNA) alterations associated with human disorders are heteroplasmic, i.e. mutant mtDNA molecules coexist with normal ones within the cell. We addressed the possibility of intermitochondrial exchanges through histologic analyses of cybrid clones with increasing proportion of the MELAS (A3243G) mtDNA transfer RNA point mutation. MtDNA-dependent cytochrome c oxidase activity and protein composition as well as mitochondrial membrane potential appeared heterogeneous in individual cells from clonal heteroplasmic cell populations on the basis of confocal and electron microscopy. The number of defective cells increased with increasing mutation load. We conclude that in the presence of a heteroplasmic mtDNA mutation in the cell type that we studied, intermitochondrial molecular exchanges cannot provide an efficient even distribution of the complementing molecules such as wild-type mtDNA, transfer RNA, or protein. Mitochondria in these heteroplasmic cells cannot, therefore, be considered a single functional unit.