Protein complexes from the oxidative phosphorylation (OXPHOS) system are assembled with the help of proteins called assembly factors. We here delineate the function of the inner mitochondrial membrane protein TMEM70, in which mutations have been linked to OXPHOS deficiencies, using a combination of BioID, complexome profiling and coevolution analyses. TMEM70 interacts with complex I and V and for both complexes the loss of TMEM70 results in the accumulation of an assembly intermediate followed by a reduction of the next assembly intermediate in the pathway. This indicates that TMEM70 has a role in the stability of membrane-bound subassemblies or in the membrane recruitment of subunits into the forming complex. Independent evidence for a role of TMEM70 in OXPHOS assembly comes from evolutionary analyses. The TMEM70/TMEM186/TMEM223 protein family, of which we show that TMEM186 and TMEM223 are mitochondrial in human as well, only occurs in species with OXPHOS complexes. Our results validate the use of combining complexome profiling with BioID and evolutionary analyses in elucidating congenital defects in protein complex assembly.

中文翻译：

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TMEM70在复合物I和V的组装中起作用。

来自氧化磷酸化（OXPHOS）系统的蛋白质复合物借助称为组装因子的蛋白质进行组装。我们在这里描述了线粒体内部膜蛋白TMEM70的功能，其中突变已与BioPH，复杂基因组分析和协同进化分析相结合，与OXPHOS缺陷有关。TMEM70与复合物I和V相互作用，并且对于这两种复合物，TMEM70的丢失都会导致装配中间体的积聚，然后减少该途径中的下一个装配中间体。这表明TMEM70在膜结合的子组件的稳定性或亚基进入形成复合物的膜募集中具有作用。TMEM70在OXPHOS装配中的作用的独立证据来自进化分析。TMEM70 / TMEM186 / TMEM223蛋白家族，其中我们表明TMEM186和TMEM223在人类中也是线粒体的，仅在具有OXPHOS复合物的物种中发生。我们的结果验证了结合使用复杂的基因组分析与BioID和进化分析来阐明蛋白质复合物装配中的先天性缺陷的用途。