title: Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1.
abstract: Hsp70 chaperones mediate folding of proteins and prevent their misfolding and aggregation. We report here on a new kind of Hsp70 interacting protein in mitochondria, Hep1. Hep1 is a highly conserved protein present in virtually all eukaryotes. Deletion of HEP1 results in a severe growth defect. Cells lacking Hep1 are deficient in processes that need the function of mitochondrial Hsp70s, such as preprotein import and biogenesis of proteins containing FeS clusters. In the mitochondria of these cells, Hsp70s, Ssc1 and Ssq1 accumulate as insoluble aggregates. We show that it is the nucleotide-free form of mtHsp70 that has a high tendency to self-aggregate. This process is efficiently counteracted by Hep1. We conclude that Hep1 acts as a chaperone that is necessary and sufficient to prevent self-aggregation and to thereby maintain the function of the mitochondrial Hsp70 chaperones.
authors.affiliation: Adolf-Butenandt-Institut, Lehrstuhl für Physiologische Chemie, Ludwig-Maximilians-Universität München, München, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Sichting
authors.forename: Dejana
authors.initials: D
authors.lastname: Mokranjac
authors.forename: Abdussalam
authors.initials: A
authors.lastname: Azem
authors.forename: Walter
authors.initials: W
authors.lastname: Neupert
authors.forename: Kai
authors.initials: K
authors.lastname: Hell
mesh_terms: D017353:Gene Deletion; D005800:Genes, Fungal; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C090869:SSA3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
references.citation: Trends Biochem Sci. 2000 Aug;25(8):352-6
references.pmid: 10916152
references.citation: FEBS Lett. 2000 Dec 29;487(2):307-12
references.pmid: 11150530
references.citation: J Biol Chem. 2001 Mar 2;276(9):6112-8
references.pmid: 11096111
references.citation: J Mol Biol. 2001 Mar 30;307(3):815-25
references.pmid: 11273703
references.citation: J Mol Biol. 2001 Jun 29;310(1):141-56
references.pmid: 11419942
references.citation: EMBO Rep. 2001 Oct;2(10):885-90
references.pmid: 11600451
references.citation: Annu Rev Biochem. 2001;70:603-47
references.pmid: 11395418
references.citation: Adv Protein Chem. 2001;59:1-44
references.pmid: 11868269
references.citation: Science. 2002 Mar 8;295(5561):1852-8
references.pmid: 11884745
references.citation: J Biol Chem. 2002 Jun 21;277(25):22140-6
references.pmid: 11940587
references.citation: Nature. 2002 Jul 25;418(6896):387-91
references.pmid: 12140549
references.citation: Biochim Biophys Acta. 2002 Sep 2;1592(1):51-62
references.pmid: 12191768
references.citation: Cell Mol Life Sci. 2002 Oct;59(10):1658-65
references.pmid: 12475176
references.citation: EMBO J. 2003 Feb 17;22(4):816-25
references.pmid: 12574118
references.citation: EMBO J. 2003 Oct 1;22(19):4945-56
references.pmid: 14517234
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41
references.pmid: 14681378
references.citation: Cell Stress Chaperones. 2003 Winter;8(4):309-16
references.pmid: 15115283
references.citation: Nat Rev Mol Cell Biol. 2004 Oct;5(10):781-91
references.pmid: 15459659
references.citation: J Cell Biol. 1984 Aug;99(2):723-33
references.pmid: 6146630
references.citation: Mol Cell Biol. 1989 Jul;9(7):3000-8
references.pmid: 2674677
references.citation: EMBO J. 1992 Jan;11(1):63-70
references.pmid: 1740116
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2081-5
references.pmid: 1532251
references.citation: J Biol Chem. 1993 Jun 15;268(17):12730-5
references.pmid: 8509407
references.citation: J Biol Chem. 1997 Jul 18;272(29):18281-9
references.pmid: 9218467
references.citation: Mol Biol Cell. 1997 Jul;8(7):1305-16
references.pmid: 9243509
references.citation: J Biol Chem. 1997 Aug 15;272(33):20901-6
references.pmid: 9252417
references.citation: Cell. 1998 Feb 6;92(3):351-66
references.pmid: 9476895
references.citation: Trends Biochem Sci. 1998 Jun;23(6):222-7
references.pmid: 9644977
references.citation: Eur J Biochem. 1999 Jan;259(1-2):505-12
references.pmid: 9914533
references.citation: Cell. 1999 May 28;97(5):565-74
references.pmid: 10367886
references.citation: Yeast. 1999 Jul;15(10B):963-72
references.pmid: 10407276
references.citation: J Biol Chem. 2004 Nov 26;279(48):50243-9
references.pmid: 15383543
references.citation: Cell. 1994 Apr 22;77(2):249-59
references.pmid: 8168133
references.citation: EMBO J. 1994 Apr 15;13(8):1998-2006
references.pmid: 8168496
references.citation: J Biol Chem. 1995 Feb 3;270(5):2183-9
references.pmid: 7836448
references.citation: FEMS Microbiol Rev. 1995 Aug;17(1-2):159-69
references.pmid: 7669342
references.citation: J Biol Chem. 1996 Aug 2;271(31):18471-6
references.pmid: 8702492
references.citation: J Cell Biol. 1996 Aug;134(3):603-13
references.pmid: 8707841
references.citation: J Biol Chem. 1997 Jan 31;272(5):2607-14
references.pmid: 9006893
references.citation: J Mol Biol. 1997 Feb 7;265(5):541-52
references.pmid: 9048947
references.citation: EMBO J. 1997 Apr 15;16(8):1842-9
references.pmid: 9155010