title: Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70.
abstract: The role of cytosolic factors in protein targeting to mitochondria is poorly understood. Here, we show that in mammals, the cytosolic chaperones Hsp90 and Hsp70 dock onto a specialized TPR domain in the import receptor Tom70 at the outer mitochondrial membrane. This interaction serves to deliver a set of preproteins to the receptor for subsequent membrane translocation dependent on the Hsp90 ATPase. Disruption of the chaperone/Tom70 recognition inhibits the import of these preproteins into mitochondria. In yeast, Hsp70 rather than Hsp90 is used in import, and Hsp70 docking is required for the formation of a productive preprotein/Tom70 complex. We outline a novel mechanism in which chaperones are recruited for a specific targeting event by a membrane-bound receptor.
authors.affiliation: Cellular Biochemistry, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Young
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hoogenraad
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D001693:Biological Transport, Active; D019556:COS Cells; D003600:Cytosol / Q000201:enzymology; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; C489039:TOM70 protein, S cerevisiae; D000251:Adenosine Triphosphatases