title: Distinct Roles of Mic12 and Mic27 in the Mitochondrial Contact Site and Cristae Organizing System.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Ralf M
authors.initials: RM
authors.lastname: Zerbes
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Höß
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: nikolaus.pfanner@biochemie.uni-freiburg.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany. Electronic address: martin.van-der-laan@uks.eu.
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
authors.affiliation: Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bohnert
mesh_terms: D017353:Gene Deletion; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; C000610593:Mic12 protein, S cerevisiae; C000610594:Mic27 protein, S cerevisiae; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: MICOS; QIL1; Saccharomyces cerevisiae; crista junction; mitofilin