人类复合物II是连接三羧酸循环和氧化磷酸化两个基本能量产生过程的关键蛋白质复合物。由于突变缺陷已被证明会导致线粒体疾病和某些癌症。然而，该复合物的结构尚未被解析，这妨碍了对这种分子机器功能方面的全面理解。在这里，我们使用冷冻电子显微镜在存在泛醌的情况下以2.86 Å的分辨率确定了人类复合物II的结构，显示它由两个水溶性亚基SDHA和SDHB以及两个跨膜亚基SDHC和SDHD组成。此结构使我们能够提出一个电子传递路线。此外，临床相关的突变被映射到结构上。该映射提供了分子理解，以解释为什么这些变异有可能产生疾病。

Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of this molecular machine. Here, we have determined the structure of human complex II in the presence of ubiquinone at 2.86 Å resolution by cryoelectron microscopy, showing it comprises two water-soluble subunits, SDHA and SDHB, and two membrane-spanning subunits, SDHC and SDHD. This structure allows us to propose a route for electron transfer. In addition, clinically relevant mutations are mapped onto the structure. This mapping provides a molecular understanding to explain why these variants have the potential to produce disease.