Oldfors Anders, Tulinius Már
Department of Pathology, Sahlgrenska University Hospital, Goteborg, Sweden.
J Neuropathol Exp Neurol. 2003 Mar;62(3):217-27. doi: 10.1093/jnen/62.3.217.
Mitochondrial encephalomyopathies are diseases caused by defective oxidative phosphorylation (OXPHOS), and affect the nervous system and/or skeletal muscle. They have emerged as a major entity among the neurometabolic diseases of childhood with an incidence of 1 in 11,000 children, and also have a high prevalence in adults. The first pathogenic mutation of human mitochondrial DNA (mtDNA) was discovered in 1988. Since then more than 100 mutations of mtDNA have been reported, including point mutations of genes encoding transfer RNA, ribosomal RNA, and proteins, as well as large-scale deletions. The first nuclear-DNA gene mutation causing OXPHOS disease was described in 1995. Mutations in nuclear genes may affect the respiratory chain by various mechanisms. Pathogenic mutations of nuclear-DNA-encoded subunits of complex I and II have been demonstrated as have mutations of respiratory chain assembly proteins. Several nuclear genes associated with mtDNA maintenance have been found to be associated with mitochondrial disorders since mutations in these genes predispose to multiple mtDNA deletions and/or reduced copy number of mtDNA. The genotype-phenotype correlation is not yet entirely clear, but new animal models will enhance our ability to study the pathophysiology of OXPHOS disorders.
线粒体脑肌病是由氧化磷酸化（OXPHOS）缺陷引起的疾病，会影响神经系统和/或骨骼肌。它们已成为儿童神经代谢疾病中的一个主要类型，发病率为每11000名儿童中有1例，在成人中也有较高的患病率。人类线粒体DNA（mtDNA）的首个致病突变于1988年被发现。从那时起，已报道了100多种mtDNA突变，包括编码转运RNA、核糖体RNA和蛋白质的基因的点突变，以及大规模缺失。1995年描述了首个导致OXPHOS疾病的核DNA基因突变。核基因中的突变可能通过多种机制影响呼吸链。已证实复合物I和II的核DNA编码亚基的致病突变以及呼吸链组装蛋白的突变。自从发现与mtDNA维持相关的几个核基因中的突变易导致多个mtDNA缺失和/或mtDNA拷贝数减少以来，已发现这些基因与线粒体疾病有关。基因型与表型的相关性尚不完全清楚，但新的动物模型将提高我们研究OXPHOS疾病病理生理学的能力。
