title: Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins.
abstract: Mitochondria import nuclear-encoded precursor proteins to four different subcompartments. Specific import machineries have been identified that direct the precursor proteins to the mitochondrial outer membrane, inner membrane or matrix, respectively. However, a machinery dedicated to the import of mitochondrial intermembrane space (IMS) proteins has not been found so far. We have identified the essential IMS protein Mia40 (encoded by the Saccharomyces cerevisiae open reading frame YKL195w). Mitochondria with a mutant form of Mia40 are selectively inhibited in the import of several small IMS proteins, including the essential proteins Tim9 and Tim10. The import of proteins to the other mitochondrial subcompartments does not depend on functional Mia40. The binding of small Tim proteins to Mia40 is crucial for their transport across the outer membrane and represents an initial step in their assembly into IMS complexes. We conclude that Mia40 is a central component of the protein import and assembly machinery of the mitochondrial IMS.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Freiburg, Freiburg, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
authors.forename: Sylvia
authors.initials: S
authors.lastname: Pfannschmidt
authors.forename: Nils
authors.initials: N
authors.lastname: Wiedemann
authors.forename: Vera
authors.initials: V
authors.lastname: Kozjak
authors.forename: Luiza K
authors.initials: LK
authors.lastname: Sanjuán Szklarz
authors.forename: Agnes
authors.initials: A
authors.lastname: Schulze-Specking
authors.forename: Kaye N
authors.initials: KN
authors.lastname: Truscott
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
mesh_terms: D000595:Amino Acid Sequence; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C495320:MIA40 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C107250:TIM10 protein, S cerevisiae; C116366:Tim9 protein, S cerevisiae