کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2812038 | 1569296 | 2007 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Normal Levels of Wild-Type Mitochondrial DNA Maintain Cytochrome c Oxidase Activity for Two Pathogenic Mitochondrial DNA Mutations but Not for m.3243A→G Normal Levels of Wild-Type Mitochondrial DNA Maintain Cytochrome c Oxidase Activity for Two Pathogenic Mitochondrial DNA Mutations but Not for m.3243A→G](/preview/png/2812038.png)
Mitochondrial DNA (mtDNA) mutations are a common cause of human disease and accumulate as part of normal ageing and in common neurodegenerative disorders. Cells express a biochemical defect only when the proportion of mutated mtDNA exceeds a critical threshold, but it is not clear whether the actual cause of this defect is a loss of wild-type mtDNA, an excess of mutated mtDNA, or a combination of the two. Here, we show that segments of human skeletal muscle fibers harboring two pathogenic mtDNA mutations retain normal cytochrome c oxidase (COX) activity by maintaining a minimum amount of wild-type mtDNA. For these mutations, direct measurements of mutated and wild-type mtDNA molecules within the same skeletal muscle fiber are consistent with the “maintenance of wild type” hypothesis, which predicts that there is nonselective proliferation of mutated and wild-type mtDNA in response to the molecular defect. However, for the m.3243A→G mutation, a superabundance of wild-type mtDNA was found in many muscle-fiber sections with negligible COX activity, indicating that the pathogenic mechanism for this particular mutation involves interference with the function of the wild-type mtDNA or wild-type gene products.
Journal: - Volume 81, Issue 1, July 2007, Pages 189–195