title: A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria.
abstract: Mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria with the help of protein translocases. For the majority of precursor proteins, the role of the translocase of the outer membrane (TOM) and mechanisms of their transport across the outer mitochondrial membrane are well recognized. However, little is known about the mode of membrane translocation for proteins that are targeted to the intermembrane space via the redox-driven mitochondrial intermembrane space import and assembly (MIA) pathway. On the basis of the results obtained from an in organello competition import assay, we hypothesized that MIA-dependent precursor proteins use an alternative pathway to cross the outer mitochondrial membrane. Here we demonstrate that this alternative pathway involves the protein channel formed by Tom40. We sought a translocation intermediate by expressing tagged versions of MIA-dependent proteins in vivo. We identified a transient interaction between our model substrates and Tom40. Of interest, outer membrane translocation did not directly involve other core components of the TOM complex, including Tom22. Thus MIA-dependent proteins take another route across the outer mitochondrial membrane that involves Tom40 in a form that is different from the canonical TOM complex.
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gornicka
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bragoszewski
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Chroscicki
authors.affiliation: Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, D-79104 Freiburg, Germany.
authors.forename: Lena-Sophie
authors.initials: LS
authors.lastname: Wenz
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, D-37073 Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland achacinska@iimcb.gov.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chacinska
mesh_terms: D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: C495320:MIA40 protein, S cerevisiae; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C066555:Tom40 protein, S cerevisiae; D013762:Tetrahydrofolate Dehydrogenase