title: The cytosolic cochaperone Sti1 is relevant for mitochondrial biogenesis and morphology.
abstract: Most mitochondrial proteins are synthesized in the cytosol prior to their import into the organelle. It is commonly accepted that cytosolic factors are required for delivering precursor proteins to the mitochondrial surface and for keeping newly synthesized proteins in an import-competent conformation. However, the identity of such factors and their defined contribution to the import process are mostly unknown. Using a presequence-containing model protein and a site-directed photo-crosslinking approach in yeast cells we identified the cytosolic chaperones Hsp70 (Ssa1) and Hsp90 (Hsp82) as well as their cochaperones, Sti1 and Ydj1, as putative cytosolic factors involved in mitochondrial protein import. Deletion of STI1 caused both alterations in mitochondrial morphology and lower steady-state levels of a subset of mitochondrial proteins. In addition, double deletion of STI1 with the mitochondrial import factors, MIM1 or TOM20, showed a synthetic growth phenotype indicating a genetic interaction of STI1 with these genes. Moreover, recombinant cytosolic domains of the import receptors Tom20 and Tom70 were able to bind in vitro Sti1 and other cytosolic factors. In summary, our observations point to a, direct or indirect, role of Sti1 for mitochondrial functionality.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Hoda
authors.initials: H
authors.lastname: Hoseini
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Saroj
authors.initials: S
authors.lastname: Pandey
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Jores
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Germany.
authors.forename: Mirita
authors.initials: M
authors.lastname: Franz-Wachtel
authors.affiliation: Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Macek
authors.affiliation: Department Chemie, Center for Integrated Protein Science, Technische Universität München, Garching, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany.
authors.forename: Kai Stefan
authors.initials: KS
authors.lastname: Dimmer
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Germany. doron.rapaport@uni-tuebingen.de.
authors.forename: Doron
authors.initials: D
authors.lastname: Rapaport
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D003432:Cross-Linking Reagents; D003600:Cytosol / Q000378:metabolism; D017353:Gene Deletion; D005800:Genes, Fungal; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D001678:Organelle Biogenesis; D021381:Protein Transport; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C492709:MIM1 protein, S cerevisiae; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C542289:STI1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C489350:TOM20 protein, S cerevisiae; C489039:TOM70 protein, S cerevisiae; C070319:YDJ1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae
keywords: TOM complex; chaperones; import receptors; mitochondria; protein import