Distinct Roles of Mic12 and Mic27 in the Mitochondrial Contact Site and Cristae Organizing System

The mitochondrial inner membrane consists of two morphologically distinct domains, the inner boundary membrane and large invaginations termed cristae. Narrow membrane structures, the crista junctions, link these two domains. Maintenance of this elaborate architecture depends on the evolutionarily conserved mitochondrial contact site and cristae organizing system (MICOS), a multisubunit inner membrane protein complex. MICOS consists of two functional modules, a Mic60-Mic19 subcomplex that forms Mic60-mediated contact sites with the outer mitochondrial membrane and a Mic10-Mic12-Mic26-Mic27 membrane-sculpting subcomplex that contains large Mic10 oligomers. Deletion of MIC10 or MIC60 results in the loss of most crista junctions. Distinct views have been discussed about how the MICOS modules cooperate with each other. We searched for components required for the structural organization of MICOS and identified Mic12 and Mic27 as crucial factors with specific roles in MICOS complex formation. Mic27 promotes the stability of the Mic10 oligomers in the membrane-sculpting subcomplex, whereas Mic12 is required for the coupling of the two MICOS subcomplexes. We conclude that in addition to the MICOS core components Mic10 and Mic60, Mic12 and Mic27 play specific roles in the organization of the MICOS complex.