Cristae architecture is determined by an interplay of the MICOS complex and the F 1 F O ATP synthase via Mic27 and Mic10.

The inner boundary and the cristae membrane are connected by pore-like structures termed crista junctions (CJs). The MICOS complex is required for CJ formation and enriched at CJs. Here, we address the roles of the MICOS subunits Mic27 and Mic10. We observe a positive genetic interaction between Mic27 and Mic60 and deletion of Mic27 results in impaired formation of CJs and altered cristae membrane curvature. Mic27 acts in an antagonistic manner to Mic60 as it promotes oligomerization of the F ₁ F _O -ATP synthase and partially restores CJ formation in cells lacking Mic60. Mic10 impairs oligomerization of the F ₁ F _O -ATP synthase similar to Mic60. Applying complexome profiling, we observed that deletion of Mic27 destabilizes the MICOS complex but does not impair formation of a high molecular weight Mic10 subcomplex. Moreover, this Mic10 subcomplex comigrates with the dimeric F ₁ F _O -ATP synthase in a Mic27-independent manner. Further, we observed a chemical crosslink of Mic10 to Mic27 and of Mic10 to the F ₁ F _O -ATP synthase subunit e. We corroborate the physical interaction of the MICOS complex and the F ₁ F _O -ATP synthase. We propose a model in which part of the F ₁ F _O -ATP synthase is linked to the MICOS complex via Mic10 and Mic27 and by that is regulating CJ formation.
Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest associated with this manuscript.