title: Mitochondrial translocation contact sites: separation of dynamic and stabilizing elements in formation of a TOM-TIM-preprotein supercomplex.
abstract: Preproteins with N-terminal presequences are imported into mitochondria at translocation contact sites that include the translocase of the outer membrane (TOM complex) and the presequence translocase of the inner membrane (TIM23 complex). Little is known about the functional cooperation of these translocases. We have characterized translocation contact sites by a productive TOM-TIM-preprotein supercomplex to address the role of three translocase subunits that expose domains to the intermembrane space (IMS). The IMS domain of the receptor Tom22 is required for stabilization of the translocation contact site supercomplex. Surprisingly, the N-terminal segment of the channel Tim23, which tethers the TIM23 complex to the outer membrane, is dispensable for both protein import and generation of the TOM-TIM supercomplex. Tim50, with its large IMS domain, is crucial for generation but not for stabilization of the supercomplex. Thus, Tim50 functions as a dynamic factor and the IMS domain of Tom22 represents a stabilizing element in formation of a productive translocation contact site supercomplex.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Ann E
authors.initials: AE
authors.lastname: Frazier
authors.forename: Agnes
authors.initials: A
authors.lastname: Schulze-Specking
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011487:Protein Conformation; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D029701:Saccharomyces cerevisiae Proteins; C083081:TIM23 protein, S cerevisiae; D013762:Tetrahydrofolate Dehydrogenase