Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1.
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.
Sichting
Martin
M
Adolf-Butenandt-Institut, Lehrstuhl für Physiologische Chemie, Ludwig-Maximilians-Universität München, München, Germany.
Mokranjac
Dejana
D
Azem
Abdussalam
A
Neupert
Walter
W
Hell
Kai
K
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*
D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C090869:SSA3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
Trends Biochem Sci. 2000 Aug;25(8):352-6
10916152
FEBS Lett. 2000 Dec 29;487(2):307-12
11150530
J Biol Chem. 2001 Mar 2;276(9):6112-8
11096111
J Mol Biol. 2001 Mar 30;307(3):815-25
11273703
J Mol Biol. 2001 Jun 29;310(1):141-56
11419942
EMBO Rep. 2001 Oct;2(10):885-90
11600451
Annu Rev Biochem. 2001;70:603-47
11395418
Adv Protein Chem. 2001;59:1-44
11868269
Science. 2002 Mar 8;295(5561):1852-8
11884745
J Biol Chem. 2002 Jun 21;277(25):22140-6
11940587
Nature. 2002 Jul 25;418(6896):387-91
12140549
Biochim Biophys Acta. 2002 Sep 2;1592(1):51-62
12191768
Cell Mol Life Sci. 2002 Oct;59(10):1658-65
12475176
EMBO J. 2003 Feb 17;22(4):816-25
12574118
EMBO J. 2003 Oct 1;22(19):4945-56
14517234
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41
14681378
Cell Stress Chaperones. 2003 Winter;8(4):309-16
15115283
Nat Rev Mol Cell Biol. 2004 Oct;5(10):781-91
15459659
J Cell Biol. 1984 Aug;99(2):723-33
6146630
Mol Cell Biol. 1989 Jul;9(7):3000-8
2674677
EMBO J. 1992 Jan;11(1):63-70
1740116
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2081-5
1532251
J Biol Chem. 1993 Jun 15;268(17):12730-5
8509407
J Biol Chem. 1997 Jul 18;272(29):18281-9
9218467
Mol Biol Cell. 1997 Jul;8(7):1305-16
9243509
J Biol Chem. 1997 Aug 15;272(33):20901-6
9252417
Cell. 1998 Feb 6;92(3):351-66
9476895
Trends Biochem Sci. 1998 Jun;23(6):222-7
9644977
Eur J Biochem. 1999 Jan;259(1-2):505-12
9914533
Cell. 1999 May 28;97(5):565-74
10367886
Yeast. 1999 Jul;15(10B):963-72
10407276
J Biol Chem. 2004 Nov 26;279(48):50243-9
15383543
Cell. 1994 Apr 22;77(2):249-59
8168133
EMBO J. 1994 Apr 15;13(8):1998-2006
8168496
J Biol Chem. 1995 Feb 3;270(5):2183-9
7836448
FEMS Microbiol Rev. 1995 Aug;17(1-2):159-69
7669342
J Biol Chem. 1996 Aug 2;271(31):18471-6
8702492
J Cell Biol. 1996 Aug;134(3):603-13
8707841
J Biol Chem. 1997 Jan 31;272(5):2607-14
9006893
J Mol Biol. 1997 Feb 7;265(5):541-52
9048947
EMBO J. 1997 Apr 15;16(8):1842-9
9155010