title: Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane.
abstract: The majority of preproteins destined for mitochondria carry N-terminal presequences. The presequence translocase of the inner mitochondrial membrane (TIM23 complex) plays a central role in protein sorting. Preproteins are either translocated through the TIM23 complex into the matrix or are laterally released into the inner membrane. We report that the small hydrophobic protein Mgr2 controls the lateral release of preproteins. Mgr2 interacts with preproteins in transit through the TIM23 complex. Overexpression of Mgr2 delays preprotein release, whereas a lack of Mgr2 promotes preprotein sorting into the inner membrane. Preproteins with a defective inner membrane sorting signal are translocated into the matrix in wild-type mitochondria but are released into the inner membrane in Mgr2-deficient mitochondria. We conclude that Mgr2 functions as a lateral gatekeeper of the mitochondrial presequence translocase, providing quality control for the membrane sorting of preproteins.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ieva
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Schrempp
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Opaliński
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Wollweber
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Höß
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Heißwolf
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gebert
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rospert
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
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: D019204:GTP-Binding Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C082883:MGM1 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C574457:Mgr2 protein, S cerevisiae; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C083081:TIM23 protein, S cerevisiae; D019204:GTP-Binding Proteins; D008727:Methotrexate