title: Mitochondrial protein sorting: differentiation of beta-barrel assembly by Tom7-mediated segregation of Mdm10.
abstract: The mitochondrial outer membrane contains two distinct machineries for protein import and protein sorting that function in a sequential manner: the general translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex), which is dedicated to beta-barrel proteins. The SAM(core) complex consists of three subunits, Sam35, Sam37, and Sam50, that can associate with a fourth subunit, the morphology component Mdm10, to form the SAM(holo) complex. Whereas the SAM(core) complex is required for the biogenesis of all beta-barrel proteins, Mdm10 and the SAM(holo) complex play a selective role in beta-barrel biogenesis by promoting assembly of Tom40 but not of porin. We report that Tom7, a conserved subunit of the TOM complex, functions in an antagonistic manner to Mdm10 in biogenesis of Tom40 and porin. We show that Tom7 promotes segregation of Mdm10 from the SAM(holo) complex into a low molecular mass form. Upon deletion of Tom7, the fraction of Mdm10 in the SAM(holo) complex is significantly increased, explaining the opposing functions of Tom7 and Mdm10 in beta-barrel sorting. Thus the role of Tom7 is not limited to the TOM complex. Tom7 functions in mitochondrial protein biogenesis by a new mechanism, segregation of a sorting component, leading to a differentiation of beta-barrel assembly.
authors.affiliation: Institut für Biochemie und Molekularbiologie and the Fakultät für Biologie, Universität Freiburg, 79104 Freiburg.
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.forename: Michael
authors.initials: M
authors.lastname: Rissler
authors.forename: Andreas
authors.initials: A
authors.lastname: Strub
authors.forename: Dusanka
authors.initials: D
authors.lastname: Milenkovic
authors.forename: Birgit
authors.initials: B
authors.lastname: Schönfisch
authors.forename: Hanne
authors.initials: H
authors.lastname: Müller
authors.forename: Vera
authors.initials: V
authors.lastname: Kozjak
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel; D008565:Membrane Proteins / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology
chemical_list: C089419:MDM10 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D029701:Saccharomyces cerevisiae Proteins; C099634:TOM7 protein, S cerevisiae; C066555:Tom40 protein, S cerevisiae