DiMauro S, Bonilla E, Davidson M, Hirano M, Schon E A
Department of Neurology, H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University College of Physicians and Surgeons, 4-420, 630 West 168th Street, New York, NY 10032, USA.
Biochim Biophys Acta. 1998 Aug 10;1366(1-2):199-210. doi: 10.1016/s0005-2728(98)00113-3.
This review considers primary mitochondrial diseases affecting the respiratory chain. As diseases due to mitochondrial DNA defects defy traditional anatomical classifications, we have not limited our discussion to neuromuscular disorders, but have extended it to include mitochondrial encephalomyopathies. Primary mitochondrial diseases can be due to mutations in either the nuclear or the mitochondrial genome. Nuclear mutations can affect (i) genes encoding enzymatic or structural mitochondrial proteins; (ii) translocases; (iii) mitochondrial protein importation; and (iv) intergenomic signaling. We review briefly recent molecular data and outstanding questions regarding these mendelian disorders, with special emphasis on cytochrome c oxidase deficiency and coenzyme Q10 deficiency. Mitochondrial DNA mutations fall into three main categories: (i) sporadic rearrangements (deletions/duplications); (ii) maternally inherited rearrangements (duplications); and (iii) maternally inherited point mutations. We summarize the most common clinical presentations and discuss pathogenic mechanisms, which remain largely elusive. Uncertainties about pathogenesis extend to the process of cell death, although excitotoxicity in neurons and apoptosis in muscle seem to have important roles.
本综述探讨了影响呼吸链的原发性线粒体疾病。由于线粒体DNA缺陷所致疾病不符合传统的解剖学分类，我们的讨论不仅限于神经肌肉疾病，还扩展至包括线粒体脑肌病。原发性线粒体疾病可能源于核基因组或线粒体基因组的突变。核基因突变可影响：（i）编码线粒体酶蛋白或结构蛋白的基因；（ii）转位酶；（iii）线粒体蛋白导入；以及（iv）基因组间信号传导。我们简要回顾了关于这些孟德尔疾病的最新分子数据及悬而未决的问题，特别强调了细胞色素c氧化酶缺乏症和辅酶Q10缺乏症。线粒体DNA突变主要分为三类：（i）散发性重排（缺失/重复）；（ii）母系遗传重排（重复）；以及（iii）母系遗传点突变。我们总结了最常见的临床表现，并讨论了致病机制，而这些机制在很大程度上仍不清楚。尽管神经元中的兴奋性毒性和肌肉中的凋亡似乎起着重要作用，但发病机制的不确定性延伸至细胞死亡过程。
