Control of protein stoichiometry is essential for cell function. Mitochondrial oxidative phosphorylation (OXPHOS) presents a complex stoichiometric challenge as the ratio of the electron transport chain (ETC) and ATP synthase must be tightly controlled, and assembly requires coordinated integration of proteins encoded in the nuclear and mitochondrial genome. How correct OXPHOS stoichiometry is achieved is unknown. We identify the Mitochondrial Regulatory hub for respiratory Assembly (MiRA) platform, which synchronizes ETC and ATP synthase biogenesis in yeast. Molecularly, this is achieved by a stop-and-go mechanism: the uncharacterized protein Mra1 stalls complex IV assembly. Two “Go” signals are required for assembly progression: binding of the complex IV assembly factor Rcf2 and Mra1 interaction with an Atp9-translating mitoribosome induce Mra1 degradation, allowing synchronized maturation of complex IV and the ATP synthase. Failure of the stop-and-go mechanism results in cell death. MiRA controls OXPHOS assembly, ensuring correct stoichiometry of protein machineries encoded by two different genomes.

蛋白质化学计量的控制对于细胞功能至关重要。线粒体氧化磷酸化 (OXPHOS) 提出了复杂的化学计量挑战，因为必须严格控制电子传递链 (ETC) 和 ATP 合酶的比例，并且组装需要核和线粒体基因组中编码的蛋白质的协调整合。如何实现正确的 OXPHOS 化学计量尚不清楚。我们确定了呼吸组装线粒体调节中心( MiRA ) 平台，该平台可同步酵母中的 ETC 和 ATP 合酶生物合成。从分子角度来说，这是通过停停机制实现的：未表征的蛋白质 Mra1 会阻止复杂 IV 的组装。组装过程需要两个“Go”信号：复合体 IV 组装因子 Rcf2 的结合和 Mra1 与 Atp9 翻译线粒体核糖体的相互作用诱导 Mra1 降解，从而使复合体 IV 和 ATP 合酶同步成熟。走走停停机制的失败会导致细胞死亡。 MiRA控制 OXPHOS 组装，确保两个不同基因组编码的蛋白质机器的化学计量正确。