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 regulated and assembly requires coordinated integration of proteins encoded in the nuclear and mitochondrial genome. How the correct OXPHOS stoichiometry is achieved remained elusive.
The group of Nora Vögtle (B04) in collaboration with Friedel Drepper (Z01) and Oliver Einsle (A04) identified the Mitochondrial Regulatory hub for respiratory Assembly (MiRA)-platform, which synchronizes ETC and ATP synthase biogenesis. Molecularly, this is achieved by a sophisticated stop-and-go-mechanism, in which stalled complex IV assembly is overridden by signals encoded in the nuclear and the mitochondrial DNA. These two “Go” signals couple complex IV to ATP synthase biogenesis and allow their synchronized maturation.
This is the first report on how the stoichiometry of the OXPHOS machinery is achieved and it also reveals the detrimental consequences of failed stoichiometric control, which results in cell death.
Please find more information in the original publication in Developmental Cell: https://www.cell.com/developmental-cell/fulltext/S1534-5807(24)00110-2
Illustration: Nora Vögtle
