Shoubridge E A, Karpati G, Hastings K E
Department of Neurology and Neurosurgery, Montreal Neurological Institute, Quebec, Canada.
Cell. 1990 Jul 13;62(1):43-9. doi: 10.1016/0092-8674(90)90238-a.
We mapped the distribution and expression of wild-type and deleted mitochondrial DNA (mtDNA) molecules in skeletal muscle fibers of patients with mitochondrial disease. We show that ragged red fiber segments, which are characteristic histological features of these myopathies, represent focal accumulations of mitochondria containing predominantly deleted mtDNAs and that the mutant genomes are absent or extremely rare in normal fiber segments. This suggests that the mtDNA mutations play a direct role in focal mitochondrial accumulation. Although levels of wild-type mtDNAs and mRNAs in ragged red fiber segments are near normal, mitochondrial function, as revealed by cytochrome oxidase cytochemistry, is severely impaired. This suggests that the presence of mutant mtDNAs interferes with the expression of coexisting wild-type mtDNAs in these segments at a posttranscriptional level.
我们绘制了线粒体疾病患者骨骼肌纤维中野生型和缺失型线粒体DNA（mtDNA）分子的分布及表达情况。我们发现，破碎红纤维节段作为这些肌病的特征性组织学特征，代表了主要含有缺失型mtDNA的线粒体的局灶性聚集，而突变基因组在正常纤维节段中不存在或极其罕见。这表明mtDNA突变在局灶性线粒体聚集中起直接作用。尽管破碎红纤维节段中野生型mtDNA和mRNA的水平接近正常，但细胞色素氧化酶细胞化学显示线粒体功能严重受损。这表明突变型mtDNA的存在在转录后水平干扰了这些节段中共存的野生型mtDNA的表达。
