DELETIONS OF MUSCLE MITOCHONDRIAL-DNA IN PATIENTS WITH MITOCHONDRIAL MYOPATHIES
DELETIONS OF MUSCLE MITOCHONDRIAL-DNA IN PATIENTS WITH MITOCHONDRIAL MYOPATHIES
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DOI：
10.1038/331717a0
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发表时间：
1988-02-25
期刊：
影响因子：
64.8
通讯作者：
MORGANHUGHES, JA
中科院分区：
文献类型：
--
作者：
HOLT, IJ;HARDING, AE;MORGANHUGHES, JA
线粒体肌病患者肌肉线粒体代谢的体外研究已经确定了线粒体呼吸链的各种功能缺陷，主要影响成人病例中的复合物I（NADH-CoQ还原酶）或复合物III（泛喹啉-细胞色素还原酶）1 -3。这两种酶由1036个亚基组成，其中8个亚基由线粒体DNA（mtDNA）4-6编码。在家族性线粒体肌病中，与父亲相反，母亲传播的发病率增加表明这些疾病可能是由mtDNA突变引起的7，8。对该疾病患者及其亲属的白细胞mtDNA进行多重限制性内切酶分析，结果显示，在任何单一母系中，受影响和未受影响的个体之间的切割模式没有差异。当研究肌肉线粒体DNA时，发现25名患者中有9名具有两个肌肉线粒体DNA群体，其中一个具有长度高达7个酶的缺失。这些观察结果表明，线粒体DNA异质性可以发生在人类和人类疾病可能与线粒体基因组的缺陷。
In vitrostudies of muscle mitochondrial metabolism in patients with mitochondrial myopathy have identified a variety of functional defects of the mitochondrial respiratory chain, predominantly affecting complex I (NADH-CoQ reductase) or complex III (ubiquinol–cytochromecreductase) in adult cases1–3. These two enzymes consist of ∼36 subunits, eight of which are encoded by mitochondrial DNA (mtDNA)4–6. The increased incidence of maternal, as opposed to paternal, transmission in familial mitochondrial myopathy suggests that these disorders may be caused by mutations of mtDNA7,8. Multiple restriction endonuclease analysis of leukocyte mtDNA from patients with the disease, and their relatives, showed no differences in cleavage patterns between affected and unaffected individuals in any single maternal line. When muscle mtDNA was studied, nine of 25 patients were found to have two populations of muscle mtDNA, one of which had deletions of up to 7 kilobases in length. These observations demonstrate that mtDNA heteroplasmy can occur in man and that human disease may be associated with defects of the mitochondrial genome.