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Transport of proteins into mitochondria

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Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 143))

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Abbreviations

AAC:

ADP/ATP carrier

CoxIV:

Cytochrome c oxidase subunit IV

pCoxIV:

Presequence of cytochrome c oxidase subunit IV

Δψ:

inner membrane potential

DHFR:

Dihydrofolate reductase

E. coli:

Escherichia coli

GIP:

General import pore

IM:

Inner membrane

IMS:

Intermembrane space

kDa:

Kilodalton

MPP:

Mitochondrial processing peptidase

MCC:

Multiconductance channel

MSF:

Mitochondrial stimulation factor

mtHsp70:

Mitochondrial heat shock protein 70

NAC:

Nascent polypeptide-associated complex

N. crassa:

Neurospora crassa

NMR:

Nuclear magnetic reasonance

OTC:

Ornithine transcarbamylase

OM:

Outer membrane

PAGE:

Polyacrylamide gel electrophoresis

S. cerevisiae:

Saccharomyces cerevisiae

Su9-DHFR:

Fo-ATPase subunit 9-dihydrofolate reductase

TIMX:

Translocase of the inner membrane, subunit of X kDa

TOMX:

Translocase of the outer membrane, subunit of X kDa

References

  • Abe Y, Shodia T, Muto T, Mihara K, Torii H, Nishikawa S, Endo T, Kohda D (2000) Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell 100:551–560

    Article  PubMed  CAS  Google Scholar 

  • Adam A, Endres M, Sirrenberg C, Lottspeich F, Neupert W, Brunner M (1999) Tim9, a new component of the TIM22·54 translocase in mitochondria. EMBO J 18:313–319

    Article  PubMed  CAS  Google Scholar 

  • Alconada A, Kübrich M, Moczko M, Hönlinger A, Pfanner N (1995) The mitochondrial receptor complex: the small subunit Mom8b/Isp6 supports association of receptors with the general insertion pore and transfer of preproteins. Mol Cell Biol 15:6196–6205

    PubMed  CAS  Google Scholar 

  • Allison DS, Schatz G (1986) Artificial mitochondrial presequences. Proc Natl Acad Sci USA 83:9011–9015

    Article  PubMed  CAS  Google Scholar 

  • Amaya Y, Arakawa H, Takiguchi M, Ebina Y, Yokota S, Mori M (1988) A noncleavable signal for mitochondrial import of 3-oxoacyl-CoA thiolase. J Biol Chem 263:14463–14470

    PubMed  CAS  Google Scholar 

  • Argan C, Lusty CJ, Shore G (1983) Membrane and cytosolic components affecting transport of the precursor of ornithine carbamyltransferase into mitochondria. J Biol Chem 258:6667–6670.

    PubMed  CAS  Google Scholar 

  • Arnold I, Fölsch H, Neupert W, Stuart RA (1998) Two distinct and independent mitochondrial targeting signals function in the sorting of an inner membrane protein, cytochrome c 1. J Biol Chem 273:1469–1476

    Article  PubMed  CAS  Google Scholar 

  • Baker A, Schatz G (1987) Sequences from a prokaryotic genome or the mouse dihydrofolate reductase gene can restore the import of a truncated precursor protein into yeast mitochondria. Proc Natl Acad Sci USA 84:3117–3121

    Article  PubMed  CAS  Google Scholar 

  • Baker KP, Schaniel A, Vestweber D, Schatz G (1990) A yeast mitochondrial outer membrane protein essential for protein import and cell viability. Nature 348:605–609

    Article  PubMed  CAS  Google Scholar 

  • Bauer MF, Sirrenberg C, Neupert W, Brunner M (1996) Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell 87:33–41

    Article  PubMed  CAS  Google Scholar 

  • Beasley EM, Wachter C, Schatz G (1992) Putting energy into mitochondrial protein import. Curr Opin Cell Biol 4:646–651

    Article  PubMed  CAS  Google Scholar 

  • Bedwell DM, Klionsky DJ, Emr SD (1987) The yeast F1-ATPase beta subunit precursor contains functionally redundant mitochondrial protein import information. Mol Cell Biol 7:4038–4047

    PubMed  CAS  Google Scholar 

  • Blobel G (1980) Intracellular protein topogenesis. Proc Natl Acad Sci USA 77:1496–1500

    Article  PubMed  CAS  Google Scholar 

  • Blom J, Kübrich M, Rassow J, Voos W, Dekker PJ, Maarse AC, Meijer M, Pfanner N (1993) The essential yeast protein MIM44 (encoded by MPI1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane. Mol Cell Biol 13:7364–7371

    PubMed  CAS  Google Scholar 

  • Bolliger L, Deloche O, Glick BS, Georgopoulos C, Jenö P, Kronidou N, Horst M, Morishima N, Schatz G (1994) A mitochondrial homologue of bacterial GrpE interacts with mitochondrial hsp70 and is essential for viability. EMBO J 13:1998–2006

    PubMed  CAS  Google Scholar 

  • Bolliger L, Junne T, Schatz G, Lithgow T (1995) Acidic receptor domains on both sides of the outer membrane mediate translocation of precursor proteins into yeast mitochondria. EMBO J 14:6318–6326

    PubMed  CAS  Google Scholar 

  • Bömer U, Pfanner N, Dietmeier K (1996) Identification of a third yeast mitochondrial Tom protein with tetratrico peptide repeats. FEBS Lett 382:153–158

    Article  PubMed  Google Scholar 

  • Bömer U, Meijer M, Maarse AC, Hönlinger A, Dekker PJ, Pfanner N, Rassow J (1997) Multiple interactions of components mediating preprotein translocation across the inner mitochondrial membrane. EMBO J 16:2205–2216

    Article  PubMed  Google Scholar 

  • Bömer U, Maarse AC, Martin F, Geissler A, Merlin A, Schönfisch B, Meijer M, Pfanner N, Rassow J (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 J 17:4226–4237

    Article  PubMed  Google Scholar 

  • Brix J, Dietmeier K, Pfanner N (1997) Differential recognition of preproteins by the purified cytosolic domains of the mitochondrial import receptors Tom20, Tom22, and Tom70. J Biol Chem 272:20730–20735

    Article  PubMed  CAS  Google Scholar 

  • Brix J, Rüdiger S, Bukau B, Schneider-Mergener J, Pfanner N (1999) Distribution of binding sequences for the mitochondrial import receptors Tom20, Tom22, and Tom70 in a presequence-carrying preprotein and a non-cleavable preprotein. J Biol Chem 274:16522–16530

    Article  PubMed  CAS  Google Scholar 

  • Bruch MD, Hoyt DW (1992) Conformational analysis of a mitochondrial presequence derived from the F1-ATPase beta-subunit by CD and NMR spectroscopy. Biochim Biophys Acta 1159:81–93

    PubMed  CAS  Google Scholar 

  • Buchberger A, Reinstein J, Bukau B (1999) in Molecular Chaperones and Folding Catalysts. Regulation, Cellular Function and Mechanism (Bukau B, ed) pp, 609–635 Harwood Academic Publishers, Amsterdam

    Google Scholar 

  • Chauwin JF, Oster G, Glick BS (1998) Strong precursor-pore interactions constrain models for mitochondrial protein import. Biophys J 74:1732–1743

    Article  PubMed  CAS  Google Scholar 

  • Chirico W, Waters MG, Blobel G (1988) 70K heat shock related proteins stimulate protein translocation into microsomes. Nature 332:805–810

    Article  PubMed  CAS  Google Scholar 

  • Craig EA, Kramer J, Shilling J, Werner-Washburne M, Holmes S, Kosic-Smithers J, Nicolet CM (1989) SSC1, an essential member of the yeast HSP70 multigene family, encodes a mitochondrial protein. Mol Cell Biol 9:3000–3008

    PubMed  CAS  Google Scholar 

  • Crowley KS, Liao S, Worrell VE, Reinhart GD, Johnson AE (1994) Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore. Cell 78:461–471

    Article  PubMed  CAS  Google Scholar 

  • Crowley KS, Payne RM (1998) Ribosome binding to mitochondria is regulated by GTP and the transit peptide. J Biol Chem 273:17278–17285

    Article  PubMed  CAS  Google Scholar 

  • Cyr DM, Stuart RA, Neupert W (1993) A matrix ATP requirement for presequence translocation across the inner membrane of mitochondria. J Biol Chem 268:23751–23754

    PubMed  CAS  Google Scholar 

  • Davis AJ, Ryan KR, Jensen RE (1998) Tim23p contains separate and distinct signals for targeting to mitochondria and insertion into the inner membrane. Mol Biol Cell 9:2577–93

    PubMed  CAS  Google Scholar 

  • Dekker PJT, Keil P, Rassow J, Maarse AC, Pfanner N, Meijer M (1993) Identification of MIM23, a putative component of the protein import machinery of the mitochondrial inner membrane. FEBS Lett 330:66–70

    Article  PubMed  CAS  Google Scholar 

  • Dekker PJT, Pfanner N (1997) Role of mitochondrial GrpE and phosphate in the ATPase cycle of matrix Hsp70. J Mol Biol 270:321–327

    Article  PubMed  CAS  Google Scholar 

  • Dekker PJT, Martin F, Maarse AC, Bömer U, Müller H, Guiard B, Meijer M, Rassow J, Pfanner N (1997) The Tim core complex defines the number of mitochondrial translation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44. EMBO J 16:5408–5419

    Article  PubMed  CAS  Google Scholar 

  • Dekker PJT, Ryan MT, Brix J, Müller H, Hönlinger A, Pfanner N (1998) Preprotein translocase of the outer mitochondrial membrane: molecular dissection and assembly of the general import pore complex. Mol Cell Biol 18:6515–6524

    PubMed  CAS  Google Scholar 

  • Dekker PJT, Pfanner N (1999) in Molecular Chaperones and Folding Catalysts. Regulation, Cellular Function and Mechanism (Bukau B, ed) pp 235–262, Harwood Academic Publishers, Amsterdam

    Google Scholar 

  • Deshaies R, Koch B, Werner-Washburne M, Craig EA, Schekman R (1988) A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature 332:800–805

    Article  PubMed  CAS  Google Scholar 

  • Dietmeier K, Hönlinger A, Bömer U, Dekker PJ, Eckerskorn C, Lottspeich F, Kübrich M, Pfanner N (1997) Tom5 functionally links mitochondrial preprotein receptors to the general import pore. Nature 388:195–200

    Article  PubMed  CAS  Google Scholar 

  • Donzeau M, Kaldi K, Adam A, Paschen S, Wanner G, Guiard B, Bauer MF, Neupert W, Brunner M (2000) Tim23 links the inner and outer mitochondrial membranes. Cell 101:401–412

    Article  PubMed  CAS  Google Scholar 

  • Eilers M, Oppliger W, Schatz G (1987) Both ATP and an energized inner membrane are required to import a purified precursor protein into mitochondria. EMBO J 6:1073–1077

    PubMed  CAS  Google Scholar 

  • Emtage JL, Jensen RE (1993) MAS6 encodes an essential inner membrane component of the yeast mitochondrial protein import pathway. J Cell Biol 122:1003–1012

    Article  PubMed  CAS  Google Scholar 

  • Endo T, Shimada I, Roise D, Inagaki F (1989) N-terminal half of a mitochondrial presequence peptide takes a helical conformation when bound to dodecylphosphocholine micelles: a proton nuclear magnetic resonance study. J Biochem 106:396–400

    PubMed  CAS  Google Scholar 

  • Finocchiaro G, Colombo I, Garavaglia B, Gellera C, Valdameri G, Garbuglio N, Didonato S (1993) cDNA cloning and mitochondrial import of the beta-subunit of the human electron-transfer flavoprotein. Eur J Biochem 213:1003–1008

    Article  PubMed  CAS  Google Scholar 

  • Fünfschilling U, Rospert S (1999) Nascent Polypeptide-associated Complex stimulates protein import into yeast mitochondria. Mol Biol Cell 10:3289–3299

    PubMed  Google Scholar 

  • Gambill BD, Voos W, Kang PJ, Miao B, Langer T, Craig EA, Pfanner N (1993) A dual role for mitochondrial heat shock protein 70 in membrane translocation of preproteins. J Cell Biol 123:109–117

    Article  PubMed  CAS  Google Scholar 

  • Gärtner F, Bömer U, Guiard B, Pfanner N (1995) The sorting signal of cytochrome b 2 promotes early divergence from the general mitochondrial import pathway and restricts the unfoldase activity of matrix Hsp70. EMBO J 14:6043–6057

    PubMed  Google Scholar 

  • Gasser SM, Daum G, Schatz G (1982) Import of proteins into mitochondria. Energy-dependent uptake of precursors by isolated mitochondria. J Biol Chem 257:13034–13041

    PubMed  CAS  Google Scholar 

  • Gässler CS, Buchberger A, Laufen T, Mayer MP, Schröder H, Valencia A, Bukau B (1998) Mutations in the DnaK chaperone affecting interaction with the DnaJ cochaperone. Proc Natl Acad Sci USA 95:15229–15234

    Article  PubMed  Google Scholar 

  • Gaume B, Klaus C, Ungermann C, Guiard B, Neupert W, Brunner M (1998) Unfolding of preproteins upon import into mitochondria. EMBO J 17:6497–6507

    Article  PubMed  CAS  Google Scholar 

  • Geli V, Yang MJ, Suda K, Lustig A, Schatz G (1990) The MAS-encoded processing protease of yeast mitochondria. Overproduction and characterization of its two nonidentical subunits. J Biol Chem 265:19216–19222

    PubMed  CAS  Google Scholar 

  • George R, Beddoe T, Landl K, Lithgow T (1998) The yeast nascent polypeptide-associated complex initiates protein targeting to mitochondria in vivo. Proc Natl Acad Sci USA 95:2296–2301

    Article  PubMed  CAS  Google Scholar 

  • Goping IS, Millar DG, Shore GC (1995) Identification of the human mitochondrial protein import receptor, huMas20p. Complementation of Δmas20 in yeast. FEBS Lett 373:45–50

    Article  PubMed  CAS  Google Scholar 

  • Gragerov A, Zeng L, Zhao X, Burkholder W, Gottesman ME (1994) Specificity of DnaK-peptide binding. J Mol Biol 235:848–854

    Article  PubMed  CAS  Google Scholar 

  • Gratzer S, Lithgow T, Bauer RE, Lamping E, Paltauf F, Kohlwein SD, Haucke V, Junne T, Schatz G, Horst M (1995) Mas37p, a novel receptor subunit for protein import into mitochondria. J Cell Biol 129:25–34

    Article  PubMed  CAS  Google Scholar 

  • Gruhler A, Ono H, Guiard B, Neupert W, Stuart RA (1995) A novel intermediate on the import pathway of cytochrome b2 into mitochondria: evidence for conservative sorting. EMBO J 14:1349–1359

    PubMed  CAS  Google Scholar 

  • Guiard B (1985) Structure, expression and regulation of a nuclear gene encoding a mitochondrial protein: the yeast (L(+)-lactate cytochrome c oxidoreductase (cytochrome b 2). EMBO J 14:3265–3272

    Google Scholar 

  • Ha J-H, Johnson ER, Mckay DB, Sousa MC, Takeda S, Wilbanks SM (1999) in Molecular Chaperones and Folding Catalysts. Regulation, Cellular Function and Mechanism (Bukau B, ed) pp 573–607, Harwood Academic Publishers, Amsterdam

    Google Scholar 

  • Hachiya N, Alam R, Sakasegawa Y, Sakaguchi M, Mihara K, Omura T (1993) A mitochondrial import factor purified from rat liver cytosol is an ATP-dependent conformational modulator for precursor proteins. EMBO J 12:1579–1586

    PubMed  CAS  Google Scholar 

  • Hachiya N, Komiya T, Alam R, Iwahashi J, Sakaguchi M, Omura T, Mihara K (1994) MSF, a novel cytoplasmic chaperone which functions in precursor targeting to mitochondria. EMBO J 13:5146–5154

    PubMed  CAS  Google Scholar 

  • Hachiya N, Mihara K, Suda K, Horst M, Schatz G, Lithgow T (1995) Reconstitution of the initial steps of mitochondrial protein import. Nature 376:705–709

    Article  PubMed  CAS  Google Scholar 

  • Hammen PK, Gorenstein DG, Weiner H (1994) Structure of the signal sequences for two mitochondrial matrix proteins that are not proteolytically processed upon import. Biochem 33:8610–8617

    Article  CAS  Google Scholar 

  • Hanson B, Nuttal S, Hoogenraad N (1996) A receptor for the import of proteins into human mitochondria. Eur J Biochem 235:750–753

    Article  PubMed  CAS  Google Scholar 

  • Harkness TA, Nargang FE, van der Klei I, Neupert W, Lill R (1994) A crucial role of the mitochondrial protein import receptor MOM19 for the biogenesis of mitochondria. J Cell Biol 124:637–648

    Article  PubMed  CAS  Google Scholar 

  • Hartl F-U, Schmidt B, Wachter E, Weiss H, Neupert W (1986) Transport into mitochondria and intramitochondrial sorting of the Fe/S protein of ubiquinolcytochrome c reductase. Cell 47:939–951

    Article  PubMed  CAS  Google Scholar 

  • Hartl F-U, Ostermann J, Guiard B, Neupert W (1987) Successive translocation into and out of the mitochondrial matrix: targeting of proteins to the intermembrane space by a bipartite signal peptide. Cell 51:1027–1037

    Article  PubMed  CAS  Google Scholar 

  • Haucke V, Lithgow T, Rospert S, Hahne K, Schatz G (1995) The yeast mitochondrial protein import receptor Mas20p binds precursor proteins through electrostatic interaction with the positively charged presequence. J Biol Chem 270:5565–5570

    Article  PubMed  CAS  Google Scholar 

  • Hill K, Model K, Ryan MT, Dietmeier K, Martin F, Wagner R, Pfanner N (1998) Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins. Nature 395:516–521

    Article  PubMed  CAS  Google Scholar 

  • Hines V, Brandt A, Griffith G, Horstmann H, Brütsch H, Schatz G (1990) Protein import into yeast mitochondria is accelerated by the outer membrane protein MAS70. EMBO J 9:3191–3200.

    PubMed  CAS  Google Scholar 

  • Hönlinger A, Kübrich M, Moczko M, Gärtner F, Mallet L, Bussereau F, Eckerskorn C, Lottspeich F, Dietmeier K, Jacquet M, Pfanner N (1995) The mitochondrial receptor complex: Mom22 is essential for cell viability and directly interacts with pre-proteins. Mol Cell Biol 15:3382–3389

    PubMed  Google Scholar 

  • Hönlinger A, Bömer U, Alconada A, Eckerskorn C, Lottspeich F, Dietmeier K, Pfanner N (1996) Tom7 modulates the dynamics of the mitochondrial outer membrane translocase and plays a pathway-related role in protein import. EMBO J 15:2125–2137

    PubMed  Google Scholar 

  • Horst M, Jenö P, Kronidou NG, Bolliger L, Oppliger, W, Scherer P, Manning-Krieg U, Jascur T, Schatz G (1993) Protein import into yeast mitochondria: the inner membrane import site protein ISP45 is the MPI1 gene product. EMBO J 12:3035–3041

    PubMed  CAS  Google Scholar 

  • Horst M, Oppliger W, Rospert S, Schonfeld HJ, Schatz G, Azem A (1997) Sequential action of two Hsp70 complexes during protein import into mitochondria. EMBO J 16:1842–1849

    Article  PubMed  CAS  Google Scholar 

  • Horwich AL, Kalousek F, Mellman I Rosenberg LE (1985) A leader peptide is sufficient to direct, mitochondrial import of a chimeric protein. EMBO J 4:1129–1135

    PubMed  CAS  Google Scholar 

  • Huang S, Ratliff KS, Schwartz MP, Spenner JM, Matouschek A (1999) Mitochondria unfold precursor proteins by unravelling them from their N-termini. Nat Struct Biol 6:1132–1138

    Article  PubMed  CAS  Google Scholar 

  • Hurt EC, Pesold-Hurt B, Schatz G (1984) The cleavable prepiece of an imported mitochondrial protein is sufficient to direct cytosolic dihydrofolate reductase into the mitochondrial matrix. FEBS Lett 178:306–310

    Article  PubMed  CAS  Google Scholar 

  • Hurt EC, Persold-Hurt B, Suda K, Oppliger W, Schatz G (1985) The first twelve amino acids (less than half of the pre-sequence) of an imported mitochondrial protein can direct mouse cytosolic dihydrofolate reductase into the yeast mitochondrial matrix. EMBO J 4:2061–2068

    PubMed  CAS  Google Scholar 

  • Hurt EC, Van Loon APMG (1986) How proteins find mitochondria and intramitochondrial compartments. Trends Biochem Sci 11:204–207

    Article  CAS  Google Scholar 

  • Hwang ST, Schatz G (1989) Translocation of proteins across the mitochondrial inner membrane, but not into the outer membrane, requires nucleoside triphosphates in the matrix. Proc Natl Acad Sci USA 86:8432–8436

    Article  PubMed  CAS  Google Scholar 

  • Hwang S, Jascur T, Vestweber D, Pon L, Schatz G (1989) Disrupted yeast mitochondria can import precursor proteins directly through their inner membrane. J Cell Biol 109:487–493

    Article  PubMed  CAS  Google Scholar 

  • Ikeda E, Yoshida S, Mitsuzawa H, Uno I, Toh-e A (1994) YGE1 is a yeast homologue of Escherichia coli grpE, and is required for maintenance of mitochondrial functions. FEBS Lett 339:265–268

    Article  PubMed  CAS  Google Scholar 

  • Isaya G, Miklos D, Rollins RA (1994) MIP1, a new yeast gene homologous to the rat mitochondrial intermediate peptidase gene, is required for oxidative metabolism in Saccharomyces cerevisiae. Mol Cell Biol 14:5603–5616

    PubMed  CAS  Google Scholar 

  • Ishihara N, Mihara K (1998) Identification of the protein import components of the rat mitochondrial inner membrane, rTIM17, rTIM23, and rTIM44. J Biochem 123:722–732

    PubMed  CAS  Google Scholar 

  • Jarosch B, Tuller G, Daum G, Waldherr M, Voskova A, Schweyen RJ (1996) Mrs5p, an essential protein of the mitochondrial intermembrane space, affects protein import into yeast mitochondria. J Biol Chem 271:17219–17225

    Article  PubMed  CAS  Google Scholar 

  • Jarvis JA, Ryan MT, Hoogenraad NJ, Craik DJ, Høj PB (1995) Solution structure of the acetylated and noncleavable mitochondrial targeting signal of rat chaperonin 10. J Biol Chem 270:1323–1331

    Article  PubMed  CAS  Google Scholar 

  • Jin H, May M, Tranebjaerg L, Kendall E, Fontan G, Jackson J, Subramony SH, Arena F, Lubs H, Smith S, Stevenson R, Schwartz C, Vetrie D (1996) A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness. Nat Genet 14:177–180

    Article  PubMed  CAS  Google Scholar 

  • Káldi K, Bauer MF, Sirrenberg C, Neupert W, Brunner M (1998) Biogenesis of Tim23 and Tim17, integral components of the TIM machinery for matrix-targeted preproteins. EMBO J 17:1569–1576

    Article  PubMed  Google Scholar 

  • Kalousek F, Isaya G, Rosenberg LE (1992) Rat liver mitochondrial intermediate peptidase (MIP): purification and initial characterization. EMBO J 11:2803–2809

    PubMed  CAS  Google Scholar 

  • Kanamori T, Nishikawa S, Shin I, Schultz PG, Endo T (1997) Probing the environment along the protein import pathways in yeast mitochondria by site-specific photocrosslinking. Proc Natl Acad Sci USA 94:485–490

    Article  PubMed  CAS  Google Scholar 

  • Kang PJ, Ostermann J, Shilling J, Neupert W, Craig EA, Pfanner N (1990) Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature 348:137–143.

    Article  PubMed  CAS  Google Scholar 

  • Kaput J, Goltz S, Blobel G (1982) Nucleotide sequence of the yeast nuclear gene for cytochrome c peroxidase precursor. Functional implications of the presequence for protein transport into mitochondria. J Biol Chem 257:15054–15058

    PubMed  CAS  Google Scholar 

  • Karslake C, Piotto ME, Pak YK, Weiner H, Gorenstein DG (1990) 2D NMR and structural model for a mitochondrial signal peptide bound to a micelle. Biochem 29:9872–9878

    Article  CAS  Google Scholar 

  • Kassenbrock CK, Cao W, Douglas MG (1993) Genetic and biochemical characterization of ISP6, a small mitochondrial outer membrane protein associated with the protein translocation complex. EMBO J 12:3023–3034

    PubMed  CAS  Google Scholar 

  • Keil P Pfanner N (1993) Insertion of MOM22 into the mitochondrial outer membrane strictly depends on surface-receptors. FEBS Lett 321:197–200

    Article  PubMed  CAS  Google Scholar 

  • Kerscher O, Holder J, Srinivasan M, Leung RS, Jensen RE (1997) The Tim54p-Tim22p complex mediates insertion of proteins into the mitochondrial inner membrane. J Cell Biol 139:1663–1675

    Article  PubMed  CAS  Google Scholar 

  • Kerscher O, Sepuri NB, Jensen RE (2000) Tim18p is a new component of the Tim54p–Tim22p translocon in the mitochondrial inner membrane. Mol Biol Cell 11:103–116

    PubMed  CAS  Google Scholar 

  • Kiebler M, Keil P, Schneider H, van der Klei IJ, Pfanner N, Neupert W (1993) The mitochondrial receptor, complex: a central role of MOM22 in mediating preprotein transfer from receptors to the general insertion pore. Cell 74:483–492

    Article  PubMed  CAS  Google Scholar 

  • Koehler CM, Merchant S, Oppliger W, Schmid K, Jarosch E, Dolfini L, Junne T, Schatz G, Tokatlidis K (1998a) Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins. EMBO J 17:6477–6486

    Article  PubMed  CAS  Google Scholar 

  • Koehler CM, Jarosch E, Tokatlidis K, Schmid K, Schweyen RJ, Schatz G (1998b) Import of mitochondrial carriers mediated by essential proteins of the intermembrane space. Science 279:369–373

    Article  PubMed  CAS  Google Scholar 

  • Koehler CM, Leuenberger D, Merchant S, Renold A, Junne T, Schatz G (1999) Human deafness dystonia is a mitochondrial disease. Proc Natl Acad Sci USA 96:2141–2146

    Article  PubMed  CAS  Google Scholar 

  • Koehler CM, Murphy MP Bally NA, Leuenberger D, Oppliger W, Dolfini L, Junne T, Schatz G, Or E (2000) Tim18p, a new subunit of the TIM22 complex that mediates insertion of imported proteins into the yeast mitochondrial inner membrane. Mol Cell Biol 20:1187–1193

    Article  PubMed  CAS  Google Scholar 

  • Koll H, Guiard B, Rassow J, Ostermann J, Horwich AL, Neupert W, Hartl F-U (1992) Antifolding activity of hsp60 couples protein import into the mitochondrial matrix with export to the intermembrane space. Cell 68:1163–1175

    Article  PubMed  CAS  Google Scholar 

  • Komiya T, Sakaguchi M, Mihara K (1996) Cytoplasmic chaperones determine the targeting pathway of precursor proteins to mitochondria. EMBO J 15:399–407

    PubMed  CAS  Google Scholar 

  • Komiya T, Rospert S, Schatz G, Mihara K (1997) Binding of mitochondrial precursor proteins to the cytoplasmic domains of the import receptors Tom70 and Tom20 is determined by cytoplasmic chaperones. EMBO J 16:4267–4275

    Article  PubMed  CAS  Google Scholar 

  • Komiya T, Rospert S Koehler C, Looser R, Schatz G, Mihara K (1998) Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: evidence for the ‘acid chain’ hypothesis. EMBO J 17:3886–3898

    Article  PubMed  CAS  Google Scholar 

  • Krimmer T, Rassow J, Kunau W-H Voos W, Pfanner N (2000) Mitochondrial protein import motor: the ATPase domain of matrix Hsp70 is crucial for binding to Tim44, while the peptide binding domain and the carboxy-terminal segment play a stimulatory role. Mol Cell Biol 20:5879–5887

    Article  PubMed  CAS  Google Scholar 

  • Kronidou NG, Oppliger W, Bolliger L, Hannavy K, Glick BS, Schatz G, Horst M (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

    Article  PubMed  CAS  Google Scholar 

  • Kübrich M, Keil P, Rassow J, Dekker PJ, Blom J, Meijer M, Pfanner N (1994) The polytopic mitochondrial inner membrane proteins MIM17 and MIM23 operate at the same preprotein import site. FEBS Lett 349:222–228

    Article  PubMed  Google Scholar 

  • Künkele KP, Heins S, Dembowski M, Nargang FE, Benz R, Thieffry M, Walz J, Lill R, Nussberger S, Neupert W (1998) The preprotein translocation channel of the outer membrane of mitochondria. Cell 93:1009–1019

    Article  PubMed  Google Scholar 

  • Kurz M, Martin H, Rassow J, Pfanner N, Ryan MT (1999) Biogenesis of Tim proteins of the mitochondrial carrier import pathway: differential targeting mechanisms and crossing-over with the main import pathway. Mol Biol Cell 10:2461–2474

    PubMed  CAS  Google Scholar 

  • Lalorya S, Gambill BD, Craig EA (1994) A role for a eukaryotic GrpE-related protein Mge1p, in protein translocation. Proc Natl Acad Sci USA 91:6481–6485

    Article  Google Scholar 

  • Lalorya S, Dekker PJT, Voos W, Craig EA, Pfanner N (1995) Mitochondrial GrpE modulates the function of matrix Hsp70 in translocation and maturation of preproteins. Mol Cell Biol 15:7098–7105

    Google Scholar 

  • Landry SJ, Jordan R, McMacken R, Gierasch LM (1992) Different conformations for the same polypeptide bound to chaperones DnaK and GroEL. Nature 355:455–457

    Article  PubMed  CAS  Google Scholar 

  • Lemire BD, Fankhauser C, Baker A, Schatz G (1989) The mitochondrial targeting function of randomly generated peptide sequences correlates with predicted helical amphiphilicity. J Biol Chem 264:20206–20215

    PubMed  CAS  Google Scholar 

  • Leuenberger D, Bally NA, Schatz G, Koehler CM (1999) Different import pathways through the mitochondrial intermembrane space for inner membrane proteins. EMBO J 18:4816–4822

    Article  PubMed  CAS  Google Scholar 

  • Lithgow T, Junne T, Suda K, Gratzer S, Schatz G (1994) The mitochondrial outer membrane protein Mas22p is essential for protein import and viability of yeast. Proc Natl Acad Sci USA 91:11973–11977

    Article  PubMed  CAS  Google Scholar 

  • Lohret TA, Jensen RE, Kinnally KW (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

    Article  PubMed  CAS  Google Scholar 

  • Maarse AC, Blom J, Grivell LA, Meijer M (1992) MPI1, an essential gene encoding a mitochondrial membrane protein, is possibly involved in protein import into yeast mitochondria. EMBO J 11:3619–3628

    PubMed  CAS  Google Scholar 

  • Maarse AC, Blom J, Keil P Pfanner N, Meijer M (1994) Identification of the essentia yeast protein MIM17, an integral mitochondrial inner membrane protein involved in protein import. FEBS Lett 349:215–221

    Article  PubMed  CAS  Google Scholar 

  • Mahlke K, Pfanner N, Martin J, Horwich AL, Hartl FU, Neupert W (1990) Sorting pathways of mitochondrial inner membrane proteins. Eur J Biochem 192:551–555

    Article  PubMed  CAS  Google Scholar 

  • Martin J, Mahlke K, Pfanner N (1991) Role of an energized inner membrane in mitochondrial protein import. J Biol Chem 266:18051–18057

    PubMed  CAS  Google Scholar 

  • Matouschek A, Azem A, Ratliff K, Glick BS, Schmid K, Schatz G (1997) Active unfolding of precursor proteins during mitochondrial protein import. EMBO J 16:6727–6736

    Article  PubMed  CAS  Google Scholar 

  • Mayer A, Nargang FE, Neupert W, Lill R (1995) MOM22 is a receptor for mitochondrial targeting sequences and cooperates with MOM19. EMBO J 14:4204–4211

    PubMed  CAS  Google Scholar 

  • Merlin A, Voos W, Maarse AC, Meijer M, Pfanner N, Rassow J (1999) 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. J Cell Biol 145:961–972

    Article  PubMed  CAS  Google Scholar 

  • Miao B, Davis JE, Craig EA (1997) Mge1 functions as a nucleotide release factor for Ssc1, a mitochondrial Hsp70 of Saccharomyces cerevisiae. J Mol Biol 265:541–552

    Article  PubMed  CAS  Google Scholar 

  • Miller DM, Delgado R, Chirgwin JM, Hardies SC, Horowitz PM (1991) Expression of cloned bovine adrenal rhodanese. J Biol Chem 266:4686–4691

    PubMed  CAS  Google Scholar 

  • Miura S, Mori M, Tatibana M (1983) Transport of ornithine carbamoyltransferase precursor into mitochondria. J Biol Chem 258:6671–6674

    PubMed  CAS  Google Scholar 

  • Moczko M, Ehmann B, Gärtner F, Hönlinger A, Schäfer E, Pfanner N (1994) Deletion of the receptor MOM19 strongly impairs import of cleavable preproteins into Saccharomyces cerevisiae mitochondria. J Biol Chem 269:9045–9051

    PubMed  CAS  Google Scholar 

  • Moczko M, Bömer U, Kübrich M, Zufall N, Hönlinger A, Pfanner N (1997) The intermembrane space domain of mitochondrial Tom22 functions as a trans binding site for preproteins with N-terminal targeting sequences. Mol Cell Biol 17:6574–6584

    PubMed  CAS  Google Scholar 

  • Murakami H, Pain D, Blobel G (1988) 70-kD heat shock-related protein is one of at least two distinct cytosolic factors stimulating protein import into mitochondria. J Cell Biol 107:2051–2057

    Article  PubMed  CAS  Google Scholar 

  • Murakami K, Mori M (1990) Purified presequence binding factor (PBF) forms an import-competent complex with a purified mitochondrial precursor protein. EMBO J 9:3201–3208

    PubMed  CAS  Google Scholar 

  • Miura S, Mori M, Tatibana M (1983) Transport of ornithine carbamoyltransferase precursor into mitochondria. J Biol Chem 258:6671–6674.

    PubMed  CAS  Google Scholar 

  • Nakai M, Kato Y, Toh-e A, Endo T (1994) Y ge1p, a eukaryotic GrpE-homologue, is localized in the mitochondrial matrix and interacts with mitochondrial hsp70. Biochem Biophys Res Commun 200:435–442

    Article  PubMed  CAS  Google Scholar 

  • Nakai M, Endo T (1995) Identification of yeast MAS17 encoding the functional counterpart of the mitochondrial receptor complex protein MOM22 of Neurospora crassa. FEBS Lett 357:202–206

    Article  PubMed  CAS  Google Scholar 

  • Nargang FE, Künkele KP, Mayer A, Ritzel RG, Neupert W, Lill R (1995) 'sheltered disruption’ of Neurospora crassa MOM22, an essential component of the mitochondrial protein import complex. EMBO J 14:1099–1108

    PubMed  CAS  Google Scholar 

  • Neupert W (1997) Protein import into mitochondria. Annu Rev Biochem 66:863–917

    Article  PubMed  CAS  Google Scholar 

  • Ohta S, Schatz G (1984) A purified precursor polypeptide requires a cytosolic protein fraction for import into mitochondria. EMBO J 3:651–657

    PubMed  CAS  Google Scholar 

  • Ohba M, Schatz G (1987) Disruption of the outer membrane restores protein import to trypsin-treated yeast mitochondria. EMBO J 6:2117–2122

    PubMed  CAS  Google Scholar 

  • Ono H, Tubio S (1988) The cytosolic factor required for import of precursors of mitochondrial proteins into mitochondria. J Biol Chem 263:3188–3193

    PubMed  CAS  Google Scholar 

  • Ono H, Tuboi S (1990) Purification and identification of a cytosolic factor required for import of precursors of mitochondrial proteins into mitochondria. Arch Biochem Biophys 280:299–304

    Article  PubMed  CAS  Google Scholar 

  • Pfanner N (2000) Recognizing mitochondrial presequences. Curr Biol 10:412–415

    Article  Google Scholar 

  • Pfanner N, Neupert W (1985) Transport of proteins into mitochondria: a potassium diffusion potential is able to drive the import of the ADP/ATP carrier. EMBO J 4:2819–2825

    PubMed  CAS  Google Scholar 

  • Pfanner N, Neupert W (1986) Transport of F1-ATPase subunit β into mitochondria depends on both a membrane potential and nucleoside triphosphates. FEBS Lett 209:152–156

    Article  PubMed  CAS  Google Scholar 

  • Pfanner N, Neupert W (1987) Distinct steps in the import of the ADP/ATP carrier into mitochondria. J Biol Chem 262:7528–7536

    PubMed  CAS  Google Scholar 

  • Pfanner N, Hoeben P, Tropschug M, Neupert W (1987a) The carboxy terminal two-thirds of the ADP/ATP carrier polypeptide contains sufficient information to direct translocation into mitochondria. J Biol Chem 262:14851–14854

    PubMed  CAS  Google Scholar 

  • Pfanner N, Müller HK, Harmey MA, Neupert W (1987b) Mitochondrial protein import: involvement of the mature part of a cleavable precursor protein in the binding to receptor sites. EMBO J 6:3449–3454

    PubMed  CAS  Google Scholar 

  • Pfanner N, Tropschug M, Neupert W (1987c) Mitochondrial protein import: nucleoside triphosphates are involved in conferring import-competence to precursors. Cell 49:815–823

    Article  PubMed  CAS  Google Scholar 

  • Pfanner N, Rassow J, Guiard B, Söllner T, Hartl FU, Neupert W (1990) Energy requirements for unfolding and membrane translocation of precursor proteins during import into mitochondria. J Biol Chem 265:16324–16329

    PubMed  CAS  Google Scholar 

  • Pohlmeyer K, Soll J, Steinkamp T, Hinnah S, Wagner R (1997) Isolation and characterization of an amino acid-selective channel protein present in the chloroplastic outer envelope membrane. Proc Natl Acad Sci USA 94:9504–9509

    Article  PubMed  CAS  Google Scholar 

  • Ramage L, Junne T, Hahne K, Lithgow T, Schatz G (1993) Functional cooperation of mitochondrial protein import receptors in yeast. EMBO J 12:4115–4123

    PubMed  CAS  Google Scholar 

  • Rapaport D, Mayer A, Neupert W, Lill R (1998) Cis and trans sites of the TOM complex of mitochondria in unfolding and initial translocation of preproteins. J Biol Chem 273:8806–8813

    Article  PubMed  CAS  Google Scholar 

  • Rassow J, Pfanner N (1991) Mitochondrial preproteins en route from the outer membrane to the inner membrane are exposed to the intermembrane space. FEBS Lett 293:85–88

    Article  PubMed  CAS  Google Scholar 

  • Rassow J, Maarse AC, Krainer E, Kübrich M, Müller H, Meijer M, Craig EA, Pfanner N (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

    Article  PubMed  CAS  Google Scholar 

  • Rassow J, von Ahsen O, Bömer U, Pfanner N (1997) Molecular chaperones: towards a characterization of the heat-shock protein 70 family. Trends Cell Biol 7:129–133

    Article  CAS  Google Scholar 

  • Rassow J, Dekker PJT, van Wilpe S, Meijer M, Soll J (1999) The preprotein translocase of the mitochondrial inner membrane: function and evolution. J Mol Biol 286:105–120

    Article  PubMed  CAS  Google Scholar 

  • Reid GA, Yonetani T, Schatz G (1982) Import of proteins into mitochondria. Import and maturation of the mitochondrial intermembrane space enzymes cytochrome b 2 and cytochrome c peroxidase in intact yeast cells. J Biol Chem 257:13068–13074

    PubMed  CAS  Google Scholar 

  • Roise D, Schatz G (1988) Mitochondrial presequences. J Biol Chem 263:4509–4511

    PubMed  CAS  Google Scholar 

  • Rojo EE, Stuart RA, Neupert W (1995) Conservative sorting of Fo-ATPase subunit 9: export from matrix requires delta pH across inner membrane and matrix ATP. EMBO J 14:3445–3451

    PubMed  CAS  Google Scholar 

  • Rospert S, Junne T, Glick BS, Schatz G (1993) Cloning and disruption of the gene encoding yeast mitochondrial chaperonin 10, the homologue of E. coli groES. FEBS Lett 335:358–360

    Article  PubMed  CAS  Google Scholar 

  • Rüdiger S, Germeroth L, Schneider-Mergener J, Bukau B (1997) Substrate specificity of the DnaK chaperone determined by screening cellulose-bound peptide libraries. EMBO J 16:1501–1507

    Article  PubMed  Google Scholar 

  • Ryan KR, Jensen RE (1993) Mas6p can be cross-linked to an arrested precursor and interacts with other proteins during mitochondrial protein import. J Biol Chem 268:23743–23746

    PubMed  CAS  Google Scholar 

  • Ryan KR, Menold MM, Garrett S, Jensen RE (1994a) SMS1, a high-copy suppressor of the yeast mas6 mutant, encodes an essential inner membrane protein required for mitochondrial protein import. Mol Biol Cell 5:529–538

    PubMed  CAS  Google Scholar 

  • Ryan MT, Hoogenraad NJ, Høj PB (1994b) Isolation of a cDNA clone specifying rat chaperonin 10, a stress-inducible mitochondrial matrix protein synthesised without a cleavable presequence. FEBS Lett 337:152–156

    Article  PubMed  CAS  Google Scholar 

  • Ryan KR, Leung RS, Jensen RE (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

    PubMed  CAS  Google Scholar 

  • Ryan MT, Müller H, Pfanner N (1999) Functional staging of ADP/ATP carrier translocation across the outer mitochondrial membrane. J Biol Chem 274:20619–20627

    Article  PubMed  CAS  Google Scholar 

  • Schatz G (1997) Just follow the acid chain. Nature 388:121–122

    Article  PubMed  CAS  Google Scholar 

  • Scherer PE, Krieg UC, Hwang ST, Vestweber D, Schatz G (1990) A precursor protein partly translocated into yeast mitochondria is bound to a 70 kD mitochondrial stress protein. EMBO J 9:4315–4322

    PubMed  CAS  Google Scholar 

  • Scherer PE, Manning-Krieg UC, Jenö P, Schatz G, Horst M (1992) Identification of a 45-kDa protein import site of the yeast mitochondrial inner membrane. Proc Natl Acad Sci USA 89:11930–11934

    Article  PubMed  CAS  Google Scholar 

  • Schleyer M, Neupert W (1985) Transport of proteins into mitochondria: Translocational intermediates spanning contact sites between outer and inner membranes. Cell 43:339–350

    Article  PubMed  CAS  Google Scholar 

  • Schleyer M, Schmidt B, Neupert W (1982) Requirement of a membrane potential for the postranslational transfer of proteins into mitochondria. Eur J Biochem 125:109–116

    Article  PubMed  CAS  Google Scholar 

  • Schlossmann J, Dietmeier K, Pfanner N, Neupert W (1994) Specific recognition of mitochondrial preproteins by the cytosolic domain of the import receptor MOM72. J Biol Chem 269:11893–11901

    PubMed  CAS  Google Scholar 

  • Schlossmann J, Lill R, Neupert W, Court DA (1996) Tom71, a novel homologue of the mitochondrial preprotein receptor Tom70. J Biol Chem 271:17890–17895

    Article  PubMed  CAS  Google Scholar 

  • Schneider H, Söllner T, Dietmeier K, Eckerskorn C, Lottspeich F Trülzsch B Neupert W, Pfanner N (1991) Targeting of the master receptor MOM19 to mitochondria. Science 254:1659–1662

    Article  PubMed  CAS  Google Scholar 

  • Schneider H-C, Berthold J, Bauer MF, Dietmeier K, Guiard B, Brunner M, Neupert W (1994) Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature 371:768–774

    Article  PubMed  CAS  Google Scholar 

  • Schneider HC, Westermann B, Neupert W, Brunner M (1996) The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. EMBO J 15:5796–5803

    PubMed  CAS  Google Scholar 

  • Segui-Real B, Kispal G, Lill R, Neupert W (1993) Functional independence of the protein translocation machineries in mitochondrial outer and inner membranes: Passage of preproteins through the intermembrane space. EMBO J 12:2211–2218

    PubMed  CAS  Google Scholar 

  • Sepuri NB, Schulke N, Pain D (1998) GTP hydrolysis is essential for protein import into the mitochondrial matrix. J Biol Chem 273:1420–1424

    Article  PubMed  CAS  Google Scholar 

  • Sepuri NBV, Gordon DM, Pain D (1998) A GTP-dependent “Push” is generally required for efficient protein translocation across the mitochondrial inner membrane into the matrix. J Biol Chem 273:20941–20950

    Article  PubMed  CAS  Google Scholar 

  • Simon MS, Peskin CS, Oster GF (1992) What drives the translocation of proteins? Proc Natl Acad Sci USA 89:3770–3774

    Article  PubMed  CAS  Google Scholar 

  • Sirrenberg C, Bauer MF, Guiard B, Neupert W, Brunner M (1996) Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22. Nature 384:582–585

    Article  PubMed  CAS  Google Scholar 

  • Sirrenberg C, Endres M, Fölsch H, Stuart RA, Neupert W, Brunner M (1998) Carrier protein import into mitochondria mediated by the intermembrane proteins Tim 10/Mrs11 and Tim12/Mrs5. Nature 391:912–915

    Article  PubMed  CAS  Google Scholar 

  • Smagula C, Douglas MG (1988) Mitochondrial import of the ADP/ATP carrier protein in Saccharomyces cerevisiae. Sequences required for receptor binding and membrane translocation. J Biol Chem 263:6783–6790

    PubMed  CAS  Google Scholar 

  • Söllner T, Griffiths G, Pfaller R, Pfanner N, Neupert W (1989) MOM19, an import receptor for mitochondrial precursor proteins. Cell 59:1061–1070

    Article  PubMed  Google Scholar 

  • Söllner T, Pfaller R, Griffiths G, Pfanner N, Neupert W (1990) A mitochondrial import receptor for the ATP/ADP carrier. Cell 62:107–115

    Article  PubMed  Google Scholar 

  • Steger HF, Söllner T, Kiebler M, Dietmeier KA, Pfaller R, Trülzsch KS, Tropschug M, Neupert W, Pfanner N (1990) Import of the ADP/ATP carrier into mitochondria: two receptors act in parallel. J Cell Biol 111:2353–2363

    Article  PubMed  CAS  Google Scholar 

  • Steinkamp T, Hill K, Hinnah SC, Wagner R, Rohl T, Pohlmeyer K, Soll J (2000) Identification of the pore-forming region of the outer chloroplast envelope protein OEP16. J Biol Chem 275:11758–11764

    Article  PubMed  CAS  Google Scholar 

  • Suh WC, Burkholder WF, Lu CZ, Zhao X, Gottesman ME, Gross CA (1998) Interaction of the Hsp 70 molecular chaperone, DnaK, with its cochaperone DnaJ. Proc Natl Acad Sci USA 95:15223–15228

    Article  PubMed  CAS  Google Scholar 

  • Terada K, Kanazawa M, Yano M, Hanson B, Hoogenraad N, Mori M (1997) Participation of the import receptor Tom20 in protein import into mammalian mitochondria: analyses in vitro and in cultured cells. FEBS Lett 403:309–312

    Article  PubMed  CAS  Google Scholar 

  • Ungermann C, Neupert W, Cyr DM (1994) The role of Hsp70 in conferring unidirectionality on protein translocation into mitochondria. Science 266:1250–1253

    Article  PubMed  CAS  Google Scholar 

  • van Loon AP, Schatz G (1987) Transport of proteins to the mitochondrial intermembrane space: the 'sorting’ domain of the cytochrome c 1 presequence is a stoptransfer sequence specific for the mitochondrial inner membrane. EMBO J 6:2441–2448

    PubMed  Google Scholar 

  • van Wilpe S, Ryan MT, Hill K, Maarse AC, Meisinger C, Brix J, Dekker PJ, Moczko M, Wagner R, Meijer M, Guiard B, Hönlinger A, Pfanner N (1999) Tom22 is a multifunctional organiser of the mitochondrial preprotein translocase. Nature 401:485–489

    Article  PubMed  Google Scholar 

  • Vestweber D, Brunner J, Baker A, Schatz G (1989) A 42K outer-membrane protein is a component of the yeast mitochondrial protein import site. Nature 341:205–209

    Article  PubMed  CAS  Google Scholar 

  • Voisine C, Craig EA, Zufall N, von Ahsen O, Pfanner N, Voos W (1999) The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp 70. Cell 97:1–20

    Article  Google Scholar 

  • von Ahsen O, Voos W, Henninger H, Pfanner N (1995) The mitochondrial protein import machinery. Role of ATP in dissociation of the Hsp70-Mim44 complex. J Biol Chem 270:29848–29853

    Article  Google Scholar 

  • von Heijne G (1986) Mitochondrial targeting sequences may form amphipathic helices. EMBO J 5:1335–1342

    Google Scholar 

  • von Heijne G, Steppuhn, J, Herrmann RG (1989) Domain structure of mitochondrial and chloroplast targeting peptides. Eur J Biochem 180:535–545

    Article  Google Scholar 

  • Voos W, Gambill BD, Guiard B, Pfanner N, Craig EA (1993) Presequence and mature part of preproteins strongly influence the dependence of mitochondrial protein import on heat shock protein 70 in the matrix. J Cell Biol 123:119–126

    Article  PubMed  CAS  Google Scholar 

  • Voos W, Gambill BD, Laloraya S, Ang D, Craig EA, Pfanner N (1994) Mitochondrial GrpE is present in a complex with hsp 70 and preproteins in transit across membranes. Mol Cell Biol 14:6627–6634

    PubMed  CAS  Google Scholar 

  • Voos W, von Ahsen O, Müller H, Guiard B, Rassow J, Pfanner N (1996) Differential requirement for the mitochondrial Hsp70-Tim44 complex, in unfolding and translocation of preproteins. EMBO J 15:2668–2677

    PubMed  CAS  Google Scholar 

  • Wachter C, Schatz G, Glick BS (1992) Role of ATP in the intramitochondrial sorting of cytochrome c 1 and the adenine nucleotide transproter. EMBO J 11:4787–4794

    PubMed  CAS  Google Scholar 

  • Wachter C, Schatz G, Glick BS (1994) Protein import into mitochondria: the requirement for external ATP is precursor-specific whereas intramitochondrial ATP is universally needed for translocation into the matrix. Mol Biol Cell 5:465–474

    PubMed  CAS  Google Scholar 

  • Wallace DC, Murdock DG (1999) Mitochondria and dystonia: the movement disorder connection? Proc Natl Acad Sci USA 96:1817–1819

    Article  PubMed  CAS  Google Scholar 

  • Weiss C, Oppliger W, Vergères G, Demel R, Jeno P, Horst M, de Kruijff B, Schatz G, Azem A (1999) Domain structure and lipid interaction of recombinant yeast Tim44. Proc Natl Acad Sci USA 96:8890–8894

    Article  PubMed  CAS  Google Scholar 

  • Zara V, Palmieri F, Mahlke K, Pfanner N (1992) The cleavable presequence is not essential for import and assembly of the phosphate carrier of mammalian mitochondria but enhances the specificity and efficiency of import. J Biol Chem 267:12077–12081

    PubMed  CAS  Google Scholar 

  • Zhu X, Zhao X, Burkholder WF, Gragerov A, Ogata CM, Gottesman ME, Hendrickson WA (1996) Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272:1606–16014

    Article  PubMed  CAS  Google Scholar 

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  1. Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Straße 7, D-79104, Freiburg, Germany

    K. N. Truscott, N. Pfanner & W. Voos

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  1. K. N. Truscott
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Truscott, K.N., Pfanner, N., Voos, W. (2001). Transport of proteins into mitochondria. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 143. Springer, Berlin, Heidelberg. https://doi.org/10.1007/BFb0115593

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