Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth.

Invaginations of the mitochondrial inner membrane, termed cristae, are hubs for oxidative phosphorylation. The mitochondrial contact site and cristae organizing system (MICOS) and the dimeric F 1 F o -ATP synthase play important roles in controlling cristae architecture. A fraction of the MICOS core subunit Mic10 is found in association with the ATP synthase, yet it is unknown whether this interaction is of relevance for mitochondrial or cellular functions. Here, we established conditions to selectively study the role of Mic10 at the ATP synthase. Mic10 variants impaired in MICOS functions stimulate ATP synthase oligomerization like wild-type Mic10 and promote efficient inner membrane energization, adaptation to non-fermentable carbon sources, and respiratory growth. Mic10's functions in respiratory growth largely depend on Mic10^ATPsynthase, not on Mic10^MICOS. We conclude that Mic10 plays a dual role as core subunit of MICOS and as partner of the F 1 F o -ATP synthase, serving distinct functions in cristae shaping and respiratory adaptation and growth. [Display omitted] • Dual role of Mic10 of mitochondrial contact site and cristae organizing system (MICOS) • Mic10 binds to mitochondrial ATP synthase and stabilizes higher order assemblies • Oligomerization of Mic10 is required for its function in MICOS, not at ATP synthase • Mic10 binding to ATP synthase supports metabolic adaptation and respiratory growth Rampelt et al. report that the core component Mic10 of the mitochondrial contact site and cristae organizing system plays a second physiologically important role at the mitochondrial ATP synthase. Mic10 variants that selectively function at the ATP synthase promote efficient metabolic adaptation, respiratory growth, and mitochondrial inner membrane energization. [ABSTRACT FROM AUTHOR]