title: Identification of the signal directing Tim9 and Tim10 into the intermembrane space of mitochondria.
abstract: The intermembrane space of mitochondria contains the specific mitochondrial intermembrane space assembly (MIA) machinery that operates in the biogenesis pathway of precursor proteins destined to this compartment. The Mia40 component of the MIA pathway functions as a receptor and binds incoming precursors, forming an essential early intermediate in the biogenesis of intermembrane space proteins. The elements that are crucial for the association of the intermembrane space precursors with Mia40 have not been determined. In this study, we found that a region within the Tim9 and Tim10 precursors, consisting of only nine amino acid residues, functions as a signal for the engagement of substrate proteins with the Mia40 receptor. Furthermore, the signal contains sufficient information to facilitate the transfer of proteins across the outer membrane to the intermembrane space. Thus, here we have identified the mitochondrial intermembrane space sorting signal required for delivery of proteins to the mitochondrial intermembrane space.
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ and Centre for Biological Signalling Studies (BIOSS), Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Dusanka
authors.initials: D
authors.lastname: Milenkovic
authors.forename: Thomas
authors.initials: T
authors.lastname: Ramming
authors.forename: Judith M
authors.initials: JM
authors.lastname: Müller
authors.forename: Lena-Sophie
authors.initials: LS
authors.lastname: Wenz
authors.forename: Natalia
authors.initials: N
authors.lastname: Gebert
authors.forename: Agnes
authors.initials: A
authors.lastname: Schulze-Specking
authors.forename: Diana
authors.initials: D
authors.lastname: Stojanovski
authors.forename: Sabine
authors.initials: S
authors.lastname: Rospert
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
mesh_terms: D000595:Amino Acid Sequence; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D021382:Protein Sorting Signals; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C495320:MIA40 protein, S cerevisiae; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C107250:TIM10 protein, S cerevisiae; C116366:Tim9 protein, S cerevisiae; D007930:Leucine