title: Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP-dependent biogenesis pathway.
abstract: Mitochondria are separated from the remainder of the eukaryotic cell by the mitochondrial outer membrane (MOM). The MOM plays an important role in different transport processes like lipid trafficking and protein import. In yeast, the ER-mitochondria encounter structure (ERMES) has a central, but poorly defined role in both activities. To understand the functions of the ERMES, we searched for suppressors of the deficiency of one of its components, Mdm10, and identified a novel mitochondrial protein that we named Mdm10 complementing protein 3 (Mcp3). Mcp3 partially rescues a variety of ERMES-related phenotypes. We further demonstrate that Mcp3 is an integral protein of the MOM that follows a unique import pathway. It is recognized initially by the import receptor Tom70 and then crosses the MOM via the translocase of the outer membrane. Mcp3 is next relayed to the TIM23 translocase at the inner membrane, gets processed by the inner membrane peptidase (IMP) and finally integrates into the MOM. Hence, Mcp3 follows a novel biogenesis route where a MOM protein is processed by a peptidase of the inner membrane.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Sinzel
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Tao
authors.initials: T
authors.lastname: Tan
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wendling
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.affiliation: Heidelberg University Biochemistry Center, Heidelberg, Germany.
authors.forename: Cagakan
authors.initials: C
authors.lastname: Özbalci
authors.affiliation: Cell Biology, University of Bayreuth, Bayreuth, Germany.
authors.forename: Xenia
authors.initials: X
authors.lastname: Chelius
authors.affiliation: Cell Biology, University of Bayreuth, Bayreuth, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Westermann
authors.affiliation: Heidelberg University Biochemistry Center, Heidelberg, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Brügger
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Doron
authors.initials: D
authors.lastname: Rapaport
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany kai-stefan.dimmer@uni-tuebingen.de.
authors.forename: Kai Stefan
authors.identifier: 0000-0003-4535-5115
authors.initials: KS
authors.lastname: Dimmer
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018628:Gene Dosage; D015870:Gene Expression; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases / Q000378:metabolism*; D021381:Protein Transport; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D010447:Peptide Hydrolases
keywords: ERMES complex; IMP; Mdm10; mitochondria; outer membrane