Turner Carrie J, Granycome Caroline, Hurst Rachel, Pohler Elizabeth, Juhola M Katariina, Juhola Martti I, Jacobs Howard T, Sutherland Lesley, Holt Ian J
MRC Dunn Human Nutrition Unit, Wellcome Trust, Cambridge CB2 2XY, United Kingdom.
Genetics. 2005 Aug;170(4):1879-85. doi: 10.1534/genetics.105.043653. Epub 2005 Jun 8.
In this study a well-characterized pathological mutation at nucleotide position 3243 of human mitochondrial DNA was introduced into human rho(0) teratocarcinoma (NT2) cells. In cloned and mixed populations of NT2 cells heteroplasmic for the mutation, mitotic segregation toward increasing levels of mutant mitochondrial DNA always occurred. Rapid segregation was frequently followed by complete loss of mitochondrial DNA. These findings support the idea that pathological mitochondrial DNA mutations are particularly deleterious in specific cell types, which can explain some of the tissue-specific aspects of mitochondrial DNA diseases. Moreover, these findings suggest that mitochondrial DNA depletion may be an important and widespread feature of mitochondrial DNA disease.
在本研究中，人类线粒体DNA核苷酸位置3243处一个特征明确的病理性突变被导入人rho(0) 畸胎癌（NT2）细胞。在对该突变呈异质性的NT2细胞克隆群体和混合群体中，总是会发生有丝分裂分离，朝着突变型线粒体DNA水平升高的方向发展。快速分离之后常常伴随着线粒体DNA的完全丢失。这些发现支持了病理性线粒体DNA突变在特定细胞类型中特别有害的观点，这可以解释线粒体DNA疾病的一些组织特异性方面。此外，这些发现表明线粒体DNA耗竭可能是线粒体DNA疾病的一个重要且普遍的特征。
