Regulatory network of the mitochondrial contact site and cristae organizing system
Heike Rampelt1, Florian Wollweber2, Maria Bohnert3, Martin van der Laan2 and Nikolaus Pfanner1,4
1Institute of Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, 79104 Freiburg, Germany; 2Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany; 3Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 7610001, Israel; 4BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
The complex architecture of the mitochondrial inner membrane serves to enable optimal functioning of the oxidative phosphorylation system. The complexes of the respiratory chain are localized asymmetrically in inner membrane invaginations, the cristae. Cristae membranes connect to the flat inner boundary membrane via crista junctions, constricted membrane structures with high local curvature. The mitochondrial contact site and cristae organizing system (MICOS) is a widely conserved oligomeric protein complex of the inner membrane whose integrity is required for crista junction stability. Two MICOS components, Mic60 and Mic10, contribute crucial, non-redundant functions to MICOS: Mic60 forms contact sites between the inner and outer membranes and bends the membrane via an amphipathic helix; Mic10 represents the oligomeric scaffold of MICOS while also inducing membrane curvature. The MICOS components Mic26 and Mic27 belong to the apolipoprotein O family and are thought to interact with the nonbilayer phospholipid cardiolipin. We find that they regulate Mic10 oligomerization and MICOS stability in an antagonistic fashion. Surprisingly, our data demonstrate that action of Mic26 and Mic27 does not depend on cardiolipin. Instead, cardiolipin modulates Mic10 oligomerization directly. Our study reveals an intricate network of regulatory components, including proteins as well as phospholipids, whose actions balance Mic10 oligomerization within the MICOS complex.