title: Separating mitochondrial protein assembly and endoplasmic reticulum tethering by selective coupling of Mdm10.
abstract: The endoplasmic reticulum-mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we report that conserved surface areas on opposite sides of the Mdm10 β-barrel interact with SAM and ERMES, respectively. We generated point mutants to separate protein assembly (SAM) from morphology and phospholipid homeostasis (ERMES). Our study reveals that the β-barrel channel of Mdm10 serves different functions. Mdm10 promotes the biogenesis of α-helical and β-barrel proteins at SAM and functions as integral membrane anchor of ERMES, demonstrating that SAM-mediated protein assembly is distinct from ER-mitochondria contact sites.
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.|Faculty of Biology, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Ellenrieder
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Opaliński
authors.affiliation: Division of Biophysics, School of Biology/Chemistry, University of Osnabrück, Osnabrück D-49034, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Becker
authors.affiliation: Division of Biophysics, School of Biology/Chemistry, University of Osnabrück, Osnabrück D-49034, Germany.
authors.forename: Vivien
authors.initials: V
authors.lastname: Krüger
authors.affiliation: Molecular Cell Biology of Plants, University of Frankfurt, Frankfurt D-60438, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mirus
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.|Faculty of Biology, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Straub
authors.affiliation: Division of Biophysics, School of Biology/Chemistry, University of Osnabrück, Osnabrück D-49034, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ebell
authors.affiliation: Molecular Cell Biology of Plants, University of Frankfurt, Frankfurt D-60438, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Flinner
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Sebastian B
authors.initials: SB
authors.lastname: Stiller
authors.affiliation: Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette 91190, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.affiliation: Molecular Cell Biology of Plants, University of Frankfurt, Frankfurt D-60438, Germany.|Buchmann Institute of Molecular Life Sciences, Cluster of Excellence Macromolecular Complexes, University of Frankfurt, Frankfurt D-60438, Germany.
authors.forename: Enrico
authors.initials: E
authors.lastname: Schleiff
authors.affiliation: Division of Biophysics, School of Biology/Chemistry, University of Osnabrück, Osnabrück D-49034, Germany.|Life Sciences &Chemistry, Focus Area Health, Jacobs University Bremen, Bremen D-28759, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.affiliation: Institute of Biochemistry and Molecular Biology, Centre for Biochemistry and Molecular Cell Research, Faculty of Medicine, University of Freiburg, Freiburg D-79104, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg D-79104, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C089419:MDM10 protein, S cerevisiae; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins