title: Role of MINOS in mitochondrial membrane architecture: cristae morphology and outer membrane interactions differentially depend on mitofilin domains.
abstract: The mitochondrial inner membrane contains a large protein complex crucial for membrane architecture, the mitochondrial inner membrane organizing system (MINOS). MINOS is required for keeping cristae membranes attached to the inner boundary membrane via crista junctions and interacts with protein complexes of the mitochondrial outer membrane. To study if outer membrane interactions and maintenance of cristae morphology are directly coupled, we generated mutant forms of mitofilin/Fcj1 (formation of crista junction protein 1), a core component of MINOS. Mitofilin consists of a transmembrane anchor in the inner membrane and intermembrane space domains, including a coiled-coil domain and a conserved C-terminal domain. Deletion of the C-terminal domain disrupted the MINOS complex and led to release of cristae membranes from the inner boundary membrane, whereas the interaction of mitofilin with the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM) were enhanced. Deletion of the coiled-coil domain also disturbed the MINOS complex and cristae morphology; however, the interactions of mitofilin with TOM and SAM were differentially affected. Finally, deletion of both intermembrane space domains disturbed MINOS integrity as well as interactions with TOM and SAM. Thus, the intermembrane space domains of mitofilin play distinct roles in interactions with outer membrane complexes and maintenance of MINOS and cristae morphology, demonstrating that MINOS contacts to TOM and SAM are not sufficient for the maintenance of inner membrane architecture.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Ralf M
authors.initials: RM
authors.lastname: Zerbes
authors.forename: Maria
authors.initials: M
authors.lastname: Bohnert
authors.forename: David A
authors.initials: DA
authors.lastname: Stroud
authors.forename: Karina
authors.initials: K
authors.lastname: von der Malsburg
authors.forename: Anita
authors.initials: A
authors.lastname: Kram
authors.forename: Silke
authors.initials: S
authors.lastname: Oeljeklaus
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.forename: Marten
authors.initials: M
authors.lastname: Veenhuis
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
mesh_terms: D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C542160:Fcj1 protein, S cerevisiae; C573102:MIC10 protein, S cerevisiae; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins