title: The functional interaction of mitochondrial Hsp70s with the escort protein Zim17 is critical for Fe/S biogenesis and substrate interaction at the inner membrane preprotein translocase.
abstract: The yeast protein Zim17 belongs to a unique class of co-chaperones that maintain the solubility of Hsp70 proteins in mitochondria and plastids of eukaryotic cells. However, little is known about the functional cooperation between Zim17 and mitochondrial Hsp70 proteins in vivo. To analyze the effects of a loss of Zim17 function in the authentic environment, we introduced novel conditional mutations within the ZIM17 gene of the model organism Saccharomyces cerevisiae that allowed a recovery of temperature-sensitive but respiratory competent zim17 mutant cells. On fermentable growth medium, the mutant cells were prone to acquire respiratory deficits and showed a strong aggregation of the mitochondrial Hsp70 Ssq1 together with a concomitant defect in Fe/S protein biogenesis. In contrast, under respiring conditions, the mitochondrial Hsp70s Ssc1 and Ssq1 exhibited only a partial aggregation. We show that the induction of the zim17 mutant phenotype leads to strong import defects for Ssc1-dependent matrix-targeted precursor proteins that correlate with a significantly reduced binding of newly imported substrate proteins to Ssc1. We conclude that Zim17 is not only required for the maintenance of mtHsp70 solubility but also directly assists the functional interaction of mtHsp70 with substrate proteins in a J-type co-chaperone-dependent manner.
authors.affiliation: From the Institut für Biochemie und Molekularbiologie, Universität Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Lewrenz
authors.forename: Nicole
authors.initials: N
authors.lastname: Rietzschel
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
mesh_terms: D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D011498:Protein Precursors; C115913:SSQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C495990:Zim17 protein, S cerevisiae; D013455:Sulfur; D007501:Iron
keywords: Chaperone Chaperonin; Co-chaperone; Heat Shock Protein; Iron-Sulfur Protein; J-protein; Mitochondria; Protein Translocation; Regulation; Zim17
references.citation: Nat Rev Mol Cell Biol. 2010 Sep;11(9):655-67
references.pmid: 20729931
references.citation: Mol Cell Biol. 1996 Dec;16(12):7063-71
references.pmid: 8943361
references.citation: J Biol Chem. 2003 Nov 7;278(45):44457-66
references.pmid: 12941935
references.citation: Cell. 1994 Apr 22;77(2):249-59
references.pmid: 8168133
references.citation: Biochem Biophys Res Commun. 2011 May 20;408(4):589-94
references.pmid: 21530495
references.citation: J Mol Biol. 2005 Aug 5;351(1):206-18
references.pmid: 15992824
references.citation: Annu Rev Biochem. 2001;70:603-47
references.pmid: 11395418
references.citation: Nat Rev Mol Cell Biol. 2004 Oct;5(10):781-91
references.pmid: 15459659
references.citation: J Cell Biol. 2003 Nov 24;163(4):707-13
references.pmid: 14638855
references.citation: J Biol Chem. 2008 Sep 19;283(38):26098-106
references.pmid: 18632665
references.citation: J Biol Chem. 2010 Feb 12;285(7):4423-31
references.pmid: 20007714
references.citation: Nature. 2011 Jul 20;475(7356):324-32
references.pmid: 21776078
references.citation: Nat Protoc. 2009;4(5):753-66
references.pmid: 19528951
references.citation: Nat Rev Mol Cell Biol. 2010 Aug;11(8):579-92
references.pmid: 20651708
references.citation: J Mol Biol. 2012 Mar 16;417(1-2):1-12
references.pmid: 22306468
references.citation: J Biol Chem. 2006 Dec 15;281(50):38705-11
references.pmid: 17052976
references.citation: Cell Mol Life Sci. 2005 Mar;62(6):670-84
references.pmid: 15770419
references.citation: J Biol Chem. 2008 Mar 28;283(13):8318-30
references.pmid: 18227070
references.citation: J Biol Chem. 2006 May 26;281(21):14580-7
references.pmid: 16551614
references.citation: Biochim Biophys Acta. 2002 Sep 2;1592(1):51-62
references.pmid: 12191768
references.citation: EMBO Rep. 2007 Jul;8(7):664-70
references.pmid: 17571076
references.citation: FEBS Lett. 2005 Jan 17;579(2):507-11
references.pmid: 15642367
references.citation: Mol Biol Cell. 2011 Mar 1;22(5):541-54
references.pmid: 21209324
references.citation: J Biol Chem. 2004 Nov 26;279(48):50243-9
references.pmid: 15383543
references.citation: Curr Biol. 1999 Apr 22;9(8):R305-8
references.pmid: 10226023
references.citation: Methods Cell Biol. 2001;65:189-215
references.pmid: 11381594
references.citation: J Biol Chem. 2009 Jan 30;284(5):2934-2946
references.pmid: 19036727
references.citation: J Biol Chem. 2005 Nov 18;280(46):38170-6
references.pmid: 16135516
references.citation: EMBO J. 2005 Mar 9;24(5):1046-56
references.pmid: 15719019
references.citation: EMBO Rep. 2004 Jun;5(6):567-71
references.pmid: 15170475
references.citation: J Biol Chem. 2003 Aug 8;278(32):29719-27
references.pmid: 12756240
references.citation: J Biol Chem. 2006 Mar 24;281(12):7801-8
references.pmid: 16431909
references.citation: J Cell Biol. 2012 Oct 1;199(1):125-35
references.pmid: 23007651
references.citation: Mol Biol Cell. 2008 Dec;19(12):5259-66
references.pmid: 18843040
references.citation: J Biol Chem. 2008 Jun 13;283(24):16363-73
references.pmid: 18420590
references.citation: Nucleic Acids Res. 1993 Jul 11;21(14):3329-30
references.pmid: 8341614
references.citation: Annu Rev Biochem. 2007;76:723-49
references.pmid: 17263664
references.citation: Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2874-8
references.pmid: 1826368
references.citation: Gene. 1995 May 26;158(1):113-7
references.pmid: 7789793
references.citation: Cell. 1999 May 28;97(5):565-74
references.pmid: 10367886
references.citation: Biochim Biophys Acta. 2012 Sep;1823(9):1491-508
references.pmid: 22609301