The J-related segment of Tim44 is essential for cell viability: A mutant Tim44 remains in the mitochondrial import site, but inefficiently recruits mtHsp70 and impairs protein translocation

Journal of Cell Biology

Volumn 145, Issue 5, 1999, Pages 961-972

  Merlin, Alessio ^a   Voos, Wolfgang ^a   Maarse, Ammy C ^b   Meijer, Michiel ^b   Pfanner, Nikolaus ^a   Rassow, Joachim ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

^b Institute for Molecular Cell Biology   (Netherlands)

Author keywords

Hsp70; Inner membrane; Mitochondria; Protein translocation; Tim44

Indexed keywords

ADAPTOR PROTEIN; ADENOSINE TRIPHOSPHATE; HEAT SHOCK PROTEIN 70; MUTANT PROTEIN; PROTEIN PRECURSOR;

ARTICLE; CELL VIABILITY; MITOCHONDRIAL MEMBRANE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FOLDING; PROTEIN TARGETING; PROTEIN TRANSPORT; SACCHAROMYCES CEREVISIAE; YEAST;

SACCHAROMYCES CEREVISIAE;

EID: 0033620691     PISSN: 00219525     EISSN: None     Source Type: Journal    
DOI: 10.1083/jcb.145.5.961     Document Type: Article

References (84)

1. Alconada, A., F. Gärtner, A. Hönlinger, M. Kübrich, and N. Pfanner. 1995. Mitochondrial receptor complex from Neurospora crassa and Saccharomyces cerevisiae. Methods Enzymol. 260:263-287.
2. Bauer, M.F., C. Sirrenberg, W. Neupert, and M. Brunner. 1996. Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell. 87:33-41.
3. Berthold, J., M.F. Bauer, H.-C. Schneider, C. Klaus, K. Dietmeier, W. Neupert, and M. Brunner. 1995. The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ ATP driving system. Cell. 81:1085-1093.
4. Blom, J., M. Kübrich, J. Rassow, W. Voos, P.J.T. Dekker, A.C. Maarse, M. Meijer, and N. Pfanner. 1993. The essential yeast protein MIM44 (encoded by MPI1) is required at an early step of preprotein translocation across the mitochondrial inner membrane. Mat. Cell. Biol. 13:7364-7371.
5. Blom, J., P.J.T. Dekker, and M. Meijer. 1995. Functional and physical interactions of components of the yeast mitochondrial inner-membrane import machinery (MIM). Eur. J. Biochem. 232:309-314.
6. Boeke, J.D., J. Trueheart, G. Natsoulis, and G.R. Fink. 1987. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 154: 164-175.
7. Bömer, U., M. Meijer, A.C. Maarse, P.J.T. Dekker, N. Pfanner, and J. Rassow. 1997. Multiple interactions of components mediating preprotein translocation across the inner mitochondrial membrane. EMBO (Eur. Mol. Biol. Organ.) J. 16:2205-2216.
8. Bömer, U., A.C. Maarse, F. Martin, A. Geissler, A. Merlin, B. Schönfisch, M. Meijer, N. Pfanner, and J. Rassow. 1998. Separation of structural and dynamic functions of the mitochondrial translocase: Tim44 is crucial for the inner membrane import sites in translocation of tightly folded domains, but not of loosely folded preproteins. EMBO (Eur. Mol. Biol. Organ.) J. 17: 4226-4237.
9. Brodsky, J.L. 1996. Posl-translational protein translocation: not all hsc70s are created equal. Trends Biochem. Sci. 21:122-126.
10. Bukau, B., and A.L. Horwich. 1998. The Hsp70 and Hsp60 chaperone machines. Cell. 92:351-366.
11. Cheetham, M.E., and A.J. Caplan. 1998. Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones. 3:28-36.
12. Corsi, A.K., and R. Schekman. 1997 The lumenal domain of Sec63p stimulates the ATPase activity of BiP and mediates BiP recruitment to the translocon in Saccharomyces cerevisiae. J. Cell Biol. 137:1483-1493.
13. Cyr, D., T. Langer, and M. Douglas. 1994. DnaJ-like proteins: molecular chaperones and specific regulators of Hsp70. Trends Biochem. Sci. 19:176-181.
14. 2 by isolated yeast mitochondria. J. Biol. Chem. 257: 13075-13080.
15. Dekker, P.J.T., and N. Pfanner. 1997. Role of mitochondrial GrpE and phosphate in the ATPase cycle of matrix Hsp70. J. Mol. Biol. 270:321-327.
16. Dekker, P.J.T., F. Martin, A.C. Maarse, U. Bömer, H. Müller, B. Guiard, M. Meijer, J. Rassow, and N. Pfanner. 1997. The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44. EMBO (Eur. Mol. Biol. Organ.) J. 16:5408-5419.
17. Deloche, O., and C. Georgopoulos. 1996. Purification and biochemical properties of Saccharomyces cerevisiae's Mge1p, the mitochondrial cochaperone of Ssc1p. J. Biol. Chem. 271:23960-23966.
18. Deloche, O., W.L. Kelley, and C. Georgopoulos. 1997a. Structure-function analysis of the Ssc1p, Mdj1p, and Mge1p Saccharomyces cerevisiae mitochondrial proteins in Escherichia coli. J. Bact. 179:6066-6075.
19. Deloche, O., K. Liberek, M. Zylicz, and C. Georgopoulos. 1997b. Purification and biochemical properties of Saccharomyces cerevisiae Mdj1p. the mitochondrial DnaJ homologue. J. Biol. Chem. 272:28539-28544.
20. Demand, J., J. Lüders, and J. Höhfeld. 1998. The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors. Mol. Cell. Biol. 18:2023-2028.
21. Feldheim, D., J. Rothblatt, and R. Scheckman. 1992. Topology and functional domains of Sec63p, an ER membrane protein required for secretory protein translocation. mol. Cell. Biol. 12:3288-3296.
22. Freeman, B.C., M.P. Myers, R. Schumacher, and R.I. Morimoto. 1995. Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1. EMBO (Eur. Mol. Biol. Organ.) J. 14: 2281-2292.
23. Gambill, D., W. Voos, P.J. Kang, B. Miao, T. Langer, E.A. Craig, and N. Pfanner. 1993. A dual role for mitochondrial heal shock protein 70 in membrane translocation of preproteins. J. Cell Biol. 123:109-117.
24. Gaume, B., C. Klaus, C. Ungermann, B. Guiard, W. Neupert, and M. Brunner. 1998. Unfolding of preproteins upon import into mitochondria. EMBO (Eur. Mol. Biol. Organ.) J. 17:6497-6507.
25. Gietz, R.D., and A. Sugino. 1988. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast lacking six-base pair restriction sites. Gene. 74:527-534.
26. Glick, B.S. 1995. Can Hsp70 proteins act as force-generating motors? Cell. 80: 11-14.
27. 2 to the mitochondrial intermembrane space: the tightly folded heme-binding domain makes import dependent upon matrix ATP. Protein Sci. 2:1901-1917.
28. Greene, M.K., K. Maskos, and S.J. Landry. 1998. Role of the J-domain in the cooperation of hsp40 with hsp70. Proc. Natl. Acad. Sci. USA. 95:6108-6113.
29. Harrison, C.J., M. Hayer-Hartl. M.D. Liberto, F.-U. Hartl, and J. Kuriyan. 1997. Crystal structure of the nucleotide exchange factor GrpE bound to the ATPase domain of the molecular chaperone DnaK. Science. 276:431-435.
30. Hartl, F.-U. 1996. Molecular chaperones in cellular protein folding. Nature. 381: 571-580.
31. 15N magnetic resonance assignments, secondary structure, and tertiary fold of Escherichia coli DnaJ (1-78). Biochemistry. 34:5587-5596.
32. Horst, M., W. Oppliger, B. Feifel, G. Schatz, and B.S. Glick. 1996. The milochondrial protein import motor: dissociation of mitochondrial hsp70 from its membrane anchor requires ATP binding rather than ATP hydrolysis. Protein Sci. 5:759-767.
33. Jensen, R.E., and K.W. Kinnally. 1997. The mitochondrial import pathway: are precursors imported through memhrane channels? J. Bioenerg. Biomembr. 29:3-10.
34. Kang, P.J., J. Ostermann, J. Shilling, W. Neuperl, E.A. Craig, and N. Pfanner. 1990. Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature. 348:137-143.
35. Kelley, W.L. 1998. The J-domain family and the recruitment of chaperone power. Trends Biochem. Sci. 23:222-227.
36. Kronidou, N.G., W. Oppliger, L. Bolliger, K. Hannavy, B.S. Glick, G. Schatz, and M. Horst. 1994. Dynamic interaction between Isp45 and mitochondrial hsp70 in the protein import system of the yeast mitochondrial inner membrane. Proc. Natl. Acad. Sci. USA. 91:12818-12822.
37. Laloraya, S., P.J.T. Dekker, W. Voos, E.A. Craig, and N. Pfanner. 1995. Mitochondrial GrpE modulates the function of matrix Hsp70 in translocation and maturation of preproteins. Mol. Cell. Biol. 15:7098-7105.
38. Liberek, K., J. Marszalek, D. Ang, and C. Georgopoulos. 1991. Escherichia coli DnaJ and GrpE heat shock proteins jointly stimulate ATPase activity of DnaK. Proc. Natl. Acad. Sci. USA. 88:2874-2878.
39. Lohret, T.A., R.E. Jensen, and K.W. Kinnally. 1997. Tim23, a protein import component of the mitochondrial inner membrane, is required for normal activity of the multiple conductance channel, MCC. J. Cell Biol. 137:377-386.
40. Luke, M.M., A. Sutton, and K.T. Arndt. 1991. Characterization of SIS1, a Saccharomyces cerevisiae homologue of bacterial dnaJ proteins. J. Cell Biol. 114:623-638.
41. Maarse, A.C., J. Blom, L.A. Grivell, and M. Meijer. 1992. MPI1, an essential gene encoding a mitochondrial membrane protein, is possibly involved in protein import into yeasl mitochondria. EMBO (Eur. Mol. Biol. Organ.) J. 11:3619-3628.
42. Matouschek, A., A. Azem, K. Ratliff, B.S. Glick, K. Schmid, and G. Schatz. 1997. Active unfolding of precursor proteins during mitochondrial protein import. EMBO (Eur. Mol. Biol. Organ.) J. 16:6727-6736.
43. Miao, B., J.E. Davis, and E.A. Craig. 1997. Mge1 functions as a nucleotide release factor for Ssc1, a mitochondrial Hsp70 of Saccharomyces cerevisiae. J. Mol. Biol. 265:541-552.
44. Nakai, M., Y. Kato, E. Ikeda, A. Toh-e, and T. Endo. 1994. YGE1p, a eukaryotic GrpE homolog, is localized in the mitochondrial matrix and interacts with mitochondrial Hsp70. Biochem. Biophys. Res. Commun. 200:435-442.
45. Neupert, W. 1997. Protein import into mitochondria. Annu. Rev. Biochem. 66: 863-917.
46. Ohki, M., F. Tamura, S. Nishimura, and H. Uchida. 1986. Nucleotide sequence of the Escherichia coli dnaJ gene and purification of the gene product. J. Biol. Chem. 261:1778-1781.
47. Pfanner, N., and M. Meijer. 1995. Protein sorting: pulling in the proteins. Curr. Biol. 5:132-135.
48. Pfanner, N., and M. Meijer. 1997. Mitochondrial biogenesis: the Tom and Tim machine. Curr. Biol. 7:100-103.
49. Pfanner, N., E.A. Craig, and A. Hbnlinger. 1997. Mitochondrial preprotein translocase. Annu. Rev. Cell Dev. Biol. 13:25-51.
50. Pon, L., and G. Schatz. 1991. Biogenesis of yeast mitochondria. In The Molecular and Cellular Biology of the Yeast Saccharomyces cerevisiae. J.R. Broach, J. Pringle, and E. Jones. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. 333-406.
51. Rapoport, T.A., M.M. Rolls, and B. Jungnickel. 1996. Approaching the mechanism of protein transport across the ER membrane. Curr. Opin. Cell Biol. 8:499-504.
52. Rassow, J., and N. Pfanner. 1991. Mitochondrial preproteins en route from the outer membrane to the inner membrane are exposed to the intermembrane space. FEBS Lett. 293:85-88.
53. Rassow, J., and N. Pfanner. 1995. The motor of mitochondrial protein import: a mitochondrial analog of the Sec63p-Kar2p system. In 30 Years of Mitochondrial Research. E. Qagliariello and F. Palmieri, editors. Elsevier Science Publishers, Amsterdam. 113-118.
54. Rassow, J., A.C. Maarse, E. Krainer, M. Kübrich, H. Müller, M. Meijer, E.A. Craig, and N. Pfanner. 1994. Mitochondrial protein import: biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44. J. Cell Biol. 127:1547-1556.
55. Rassow, J., W. Voos, and N. Pfanner. 1995. Partner proteins determine multiple functions of Hsp70. Trends Cell Biol. 5:207-212.
56. Rassow, J., P.J.T. Dekker, S. van der Wilpe, M. Meijer, and J. Soll. 1999. The preprotein translocase of the mitochondrial inner membrane: function and evolution. J. Mol. Biol. 286:105-120.
57. Rowley, N., C. Prip-Buus, B. Westermann, C. Brown, E. Schwarz, B. Barrell, and W. Neupert. 1994. Mdj1p, a novel chaperone of the DnaJ family, is involved in mitochondrial biogenesis and protein folding. Cell. 77:249-259.
58. Ryan, K.R., and R.E. Jensen. 1995. Protein translocation across mitochondrial membranes: what a long, strange trip it is. Cell. 83:517-519.
59. Ryan, K.R., R.S. Leung, and R.E. Jensen. 1998. Characterization of the mitochondrial inner membrane translocase complex: the Tim23p hydrophobic domain interacts with Tim17p but not with other Tim23p molecules. Mol. Cell. Biol. 18:178-187.
60. Sadler, I.A., A. Chiang, T. Kurihara, J. Rothblatt, J. Way, and P. Silver. 1989. A yeast gene essential for protein assembly in the endoplasmic reticulum and the nucleus has homology to DnaJ, an E. coli heat shock protein. J. Cell Biol. 109:2665-2675.
61. Schägger, H., and G. von Jagow. 1991 Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal. Biochem. 199:223-231.
62. Schatz, G. 1996. The protein import system of mitochondria. J. Biol. Chem. 271: 31763-31766.
63. Scherer, P.E., U.C. Manning-Krieg, P. Jenö, G. Schatz, and M. Horst. 1992. Identification of a 45-kD protein at the protein import site of the yeast mitochondrial inner membrane. Proc. Natl. Acad. Sci. USA. 89:11930-11934.
64. Schlenstedt, G., S. Harris, B. Risse, R. Lill, and P. Silver. 1995. A yeast DnaJ homologue, Scj1p, can function in the endoplasmic reticulum with BiP/ Kar2p via a conserved domain that specifies interaction with Hsp70s. J. Cell Biol. 129:979-988.
65. Schneider, H.-C., J. Berthold, M.F. Bauer, K. Dietmeier, B. Guiard, M. Brunner, and W. Neupert. 1994. Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature. 371:768-774.
66. Schneider, H.-C., B. Westermann, W. Neupert, and M. Brunner. 1996. The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mtHsp70-Tim44 interaction driving mitochondrial protein import. EMBO (Eur. Mol. Biol. Organ.) J. 15:5796-5803.
67. Scidmore, M.A., H.H. Okamura, and M.D. Rose. 1993. Genetic interactions between KAR2 and SEC63, encoding eukaryotic homologues of DnaK and DnaJ in the endoplasmic reticulum. Mol. Biol. Cell. 4:1145-1159.
68. Silver, P.A., and J.C. Way. 1993. Eucaryotic DnaJ homologs and the specificity of Hsp70 activity. Cell. 74:5-6.
69. Simon, S.M., C.S. Peskin, and G.F. Oster. 1992. What drives the translocation of proteins? Proc. Natl. Acad. Sci. USA. 89:3770-3774.
70. Sims, P.J., A.S. Waggoner, C.-H. Wang, and J.F. Hoffmann. 1974. Studies on the mechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesicles. Biochemistry. 13:3315-3330.
71. Söllner, T., J. Rassow, and N. Pfanner. 1991. Analysis of mitochondrial protein import using translocation intermediates and specific antibodies. Methods Cell Biol. 34:345-357.
72. Szyperski, T., M. Pellecchia, D. Wall, C. Georgopoulos, and K. Wüthrich. 1994. NMR structure determination of the Escherichia coli DnaJ molecular chaperone: secondary structure and backbone fold of the N-terminal region (residues 2-108) containing the highly conserved J domain. Proc. Natl. Acad. Sci. USA. 91:11343-11347.
73. Ungermann, C., W. Neupert, and D.M. Cyr. 1994. The role of Hsp70 in conferring unidirectionality on protein translocation into mitochondria. Science. 266:1250-1253.
74. Ungermann, C., B. Guiard, W. Neupert, and D.M. Cyr. 1996. The Δψ- and Hsp70/MIM44-dependent reaction cycle driving early steps of protein import into mitochondria. EMBO (Eur. Mol. Biol. Organ.) J. 15:735-744.
75. Ungewickell, E., H. Ungewickell, and S.E.H. Holstein. 1997. Functional interaction of the auxilin J domain with the nucleotide- and substrate-binding modules of Hsc70. J. Biol. Chem. 272:19594-19600.
76. von Ahsen, O., W. Voos, H. Henninger, and N. Pfanner. 1995. The mitochondrial protein import machinery. Role of ATP in dissociation of the Hsp70-Mim44 complex. J. Biol. Chem. 270:29848-29853.
77. Voos, W., D. Gambill, B. Guiard, N. Pfanner, and E.A. Craig. 1993. Presequence and mature part of preproteins strongly influence the dependence of mitochondrial protein import in heat shock protein 70 in the matrix. J. Cell Biol. 123:119-126.
78. Voos, W., D. Gambill, S. Laloraya, D. Ang, E.A. Craig, and N. Pfanner. 1994. Mitochondrial GrpE is present in a complex with Hsp70 and preproteins in transit across membranes. Mol. Cell. Biol. 14:6627-6634.
79. Voos, W., O. von Ahsen, H. Müller, B. Guiard, J. Rassow, and N. Pfanner. 1996. Differential requirement for the mitochondrial Hsp70-Tim44 complex in unfolding and translocation of preproteins. EMBO (Eur. Mol. Biol. Organ.) J. 15:2668-2677.
80. Wada, J., and Y.S. Kanwar. 1998. Characterization of mammalian translocase of inner mitochondrial membrane (Tim44) isolated from diabetic newborn mouse kidney. Proc. Natl. Acad. Sci. USA. 95:144-149.
81. Westermann, B., and W. Neupert. 1997. Mdj2p, a novel DnaJ homolog in the mitochondrial inner membrane of the yeast Saccharomyces cerevisiae. J. Mol. Biol. 272:477-483.
82. Westermann, B., C. Prip-Buus, W. Neupert, and E. Schwarz. 1995. The role of the GrpE homologue, Mge1p, in mediating protein import and protein folding in mitochondria. EMBO (Eur. Mol. Biol. Organ.) J. 14:3452-3460.
83. Westermann, B., B. Gaume, J.M. Herrmann, W. Neupert, and E. Schwarz. 1996. Role of the mitochondrial DnaJ homolog Mdj1p as a chaperone for mitochondrially synthesized and imported proteins. Mol. Cell. Biol. 16:7063-7071.
84. Zhong, T., and K.T. Arndt. 1993. The yeast SIS1 protein, a DnaJ homolog, is required for the initiation of translation. Cell. 73:1175-1186.