title: Apocytochrome c requires the TOM complex for translocation across the mitochondrial outer membrane.
abstract: The import of proteins into the mitochondrial intermembrane space differs in various aspects from the classical import pathway into the matrix. Apocytochrome c defines one of several pathways known to reach the intermembrane space, yet the components and pathways involved in outer membrane translocation are poorly defined. Here, we report the reconstitution of the apocytochrome c import reaction using proteoliposomes harbouring purified components. Import specifically requires the protease-resistant part of the TOM complex and is driven by interactions of the apoprotein with internal parts of the complex (involving Tom40) and the 'trans-side receptor' cytochrome c haem lyase. Despite the necessity of TOM complex function, the translocation pathway of apocytochrome c does not overlap with that of presequence-containing preproteins. We conclude that the TOM complex is a universal preprotein translocase that mediates membrane passage of apocytochrome c and other preproteins along distinct pathways. Apocytochrome c may provide a paradigm for the import of other small proteins into the intermembrane space such as factors used in apoptosis and protection from stress.
authors.affiliation: Institut für Zytobiologie und Zytopathologie der Philipps-Universität Marburg, Robert-Koch-Strasse 5, 35033 Marburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Diekert
authors.forename: A I
authors.initials: AI
authors.lastname: de Kroon
authors.forename: U
authors.initials: U
authors.lastname: Ahting
authors.forename: B
authors.initials: B
authors.lastname: Niggemeyer
authors.forename: W
authors.initials: W
authors.lastname: Neupert
authors.forename: B
authors.initials: B
authors.lastname: de Kruijff
authors.forename: R
authors.initials: R
authors.lastname: Lill
mesh_terms: D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism*; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism*; D045304:Cytochromes c; D004875:Ergosterol / Q000494:pharmacology; D005656:Fungal Proteins / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D009492:Neurospora crassa / Q000378:metabolism; D018272:Porins / Q000187:drug effects; D021122:Protein Subunits; D021381:Protein Transport; D011510:Proteolipids / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
chemical_list: D001059:Apoproteins; D003574:Cytochrome c Group; D005656:Fungal Proteins; D008081:Liposomes; D046911:Macromolecular Substances; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D018272:Porins; D021122:Protein Subunits; D011510:Proteolipids; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C489350:TOM20 protein, S cerevisiae; C090857:TOM22 protein, S cerevisiae; C099634:TOM7 protein, S cerevisiae; C489039:TOM70 protein, S cerevisiae; C066555:Tom40 protein, S cerevisiae; C429542:Tom6 protein, Neurospora crassa; C020485:proteoliposomes; D045304:Cytochromes c; D013762:Tetrahydrofolate Dehydrogenase; D006180:Proton-Translocating ATPases; D004875:Ergosterol