Mitochondrial disorders are amongst the most frequent inborn errors of metabolism, their primary cause being the dysfunction of the oxidative phosphorylation system (OXPHOS). OXPHOS is composed of the electron transport chain (ETC), formed by four multimeric enzymes and two mobile electron carriers, plus an ATP synthase (also called complex V). The ETC performs the redox reactions involved in cellular respiration while generating the proton motive force used by complex V to synthesize ATP. OXPHOS biogenesis involves multiple steps, starting from the expression of genes encoded in physically separated genomes, namely the mitochondrial and nuclear DNA, to the coordinated assembly of components and cofactors building each individual complex and eventually the supercomplexes. The genetic cause underlying around half of the diagnosed mitochondrial disease cases is currently known. Many of these cases result from pathogenic variants in genes encoding structural subunits or additional factors directly involved in the assembly of the ETC complexes. Here we review the historical and most recent findings concerning the clinical phenotypes and the molecular pathological mechanisms underlying this particular group of disorders.

中文翻译：

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氧磷系统的线粒体疾病

线粒体疾病是最常见的先天性代谢错误之一，其主要原因是氧化磷酸化系统 (OXPHOS) 的功能障碍。OXPHOS 由电子传递链 (ETC) 组成，由四个多聚酶和两个移动电子载体以及一个 ATP 合酶（也称为复合物 V）组成。ETC 执行涉及细胞呼吸的氧化还原反应，同时产生复合物 V 用于合成 ATP 的质子动力。OXPHOS 生物发生涉及多个步骤，从在物理分离的基因组中编码的基因（即线粒体和核 DNA）的表达开始，到构建每个单独的复合体的组分和辅助因子的协调组装，最终形成超复合体。目前已知大约一半诊断出的线粒体疾病病例的遗传原因。其中许多病例是由编码结构亚基的基因的致病变异或直接参与 ETC 复合物组装的其他因素引起的。在这里，我们回顾了有关这一特定疾病组的临床表型和分子病理机制的历史和最新发现。