title: Central role of Mic10 in the mitochondrial contact site and cristae organizing system.
abstract: The mitochondrial contact site and cristae organizing system (MICOS) is a conserved multi-subunit complex crucial for maintaining the characteristic architecture of mitochondria. Studies with deletion mutants identified Mic10 and Mic60 as core subunits of MICOS. Mic60 has been studied in detail; however, topogenesis and function of Mic10 are unknown. We report that targeting of Mic10 to the mitochondrial inner membrane requires a positively charged internal loop, but no cleavable presequence. Both transmembrane segments of Mic10 carry a characteristic four-glycine motif, which has been found in the ring-forming rotor subunit of F1Fo-ATP synthases. Overexpression of Mic10 profoundly alters the architecture of the inner membrane independently of other MICOS components. The four-glycine motifs are dispensable for interaction of Mic10 with other MICOS subunits but are crucial for the formation of large Mic10 oligomers. Our studies identify a unique role of Mic10 oligomers in promoting the formation of inner membrane crista junctions.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bohnert
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Faculty of Biology, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Ralf M
authors.initials: RM
authors.lastname: Zerbes
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Davies
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Mühleip
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Rampelt
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Horvath
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Thorina
authors.initials: T
authors.lastname: Boenke
authors.affiliation: Molecular Cell Biology, University of Groningen, 9700 CC Groningen, the Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Kram
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Inge
authors.initials: I
authors.lastname: Perschil
authors.affiliation: Molecular Cell Biology, University of Groningen, 9700 CC Groningen, the Netherlands.
authors.forename: Marten
authors.initials: M
authors.lastname: Veenhuis
authors.affiliation: Department of Structural Biology, Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kühlbrandt
authors.affiliation: Molecular Cell Biology, University of Groningen, 9700 CC Groningen, the Netherlands.
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany. Electronic address: nikolaus.pfanner@biochemie.uni-freiburg.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany. Electronic address: martin.van.der.laan@biochemie.uni-freiburg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
mesh_terms: D000595:Amino Acid Sequence; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: C573102:MIC10 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins