Mitochondrial complex II (succinate:ubiquinone oxidoreductase) is the smallest complex of the oxidative phosphorylation system, a tetramer of just 140 kDa. Despite its diminutive size, it is a key complex in two coupled metabolic pathways - it oxidises succinate to fumarate in the tricarboxylic acid cycle and the electrons are used to reduce FAD to FADH_2, ultimately reducing ubiquinone to ubiquinol in the respiratory chain. The biogenesis and assembly of Complex II is facilitated by four ancillary proteins, all of which are autosomally-encoded. Numerous pathogenic defects have been reported which describe two broad clinical manifestations, either susceptibility to cancer in the case of single, heterozygous germline variants, or a mitochondrial disease presentation, almost exclusively due to bi-allelic recessive variants and associated with an isolated complex II deficiency. Here we present a compendium of pathogenic gene variants that have been documented in the literature in patients with an isolated mitochondrial complex II deficiency. To date, 62 patients are described, harbouring 32 different pathogenic variants in four distinct complex II genes: three structural subunit genes (SDHA, SDHB and SDHD) and one assembly factor gene (SDHAF1). Many pathogenic variants result in a null mutation due to nonsense, frameshift or splicing defects however, the missense variants that do occur tend to induce substitutions at highly conserved residues in regions of the proteins that are critical for binding to other subunits or substrates. There is phenotypic heterogeneity associated with defects in each complex II gene, similar to other mitochondrial diseases.

线粒体复合物II（琥珀酸酯：泛醌氧化还原酶）是氧化磷酸化系统中最小的复合物，仅为140 kDa的四聚体。尽管它的体积很小，但它是两个耦合的代谢途径中的关键复合物-它在三羧酸循环中将琥珀酸氧化为富马酸酯，并且电子用于将FAD还原为FADH _2，最终在呼吸链中将泛醌还原为泛醇。复合物II的生物发生和组装受四个辅助蛋白的促进，所有这些蛋白都是自体编码的。已经报道了许多致病性缺陷，它们描述了两种广泛的临床表现，要么是单一杂合子种系变异体对癌症的易感性，要么是线粒体疾病的表现，这几乎完全是由于双等位基因隐性变异体引起的，并伴有孤立的复合物II缺乏症。在这里，我们介绍了病原体基因变异的纲要，该文献已在文献中对线粒体复合体II缺乏症患者进行了报道。迄今为止，已描述了62名患者，它们在四个不同的复杂II基因中具有32种不同的致病变异：三个结构亚基基因SDHA，SDHB和SDHD）和一个装配因子基因（SDHAF1）。许多致病变体由于无义，移码或剪接缺陷而导致无效突变，但是，确实发生的错义变体倾向于在蛋白质区域中高度保守的残基处诱导取代，这对于与其他亚基或底物的结合至关重要。与其他线粒体疾病相似，每个复合物II基因中都有与缺陷相关的表型异质性。