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Mitochondrial Protein Import: Unfolding and Refolding of Precursor Proteins

  • Conference paper
Stress Proteins

Abstract

More than 95% of mitochondrial proteins are encoded by nuclear genes, are synthesized as precursor proteins on cytosolic polysomes, and are eventually imported into one of the four mitochondrial subcompartments (outer membrane, intermembrane space, inner membrane, and matrix) (for review see Hurt and van Loon 1986; Attardi and Schatz 1988; Pfanner et al. 1988a; Hartl et al. 1989; Pfanner and Neupert 1989). The precursor proteins carry targeting information in amino-terminal extension sequences (termed presequences) or at various positions of the mature portion of the polypeptide chain. After recognition by receptor proteins on the mitochondrial surface, the precursor proteins become inserted into the outer membrane. Insertion into and translocation across the inner mitochondrial membrane occur at contact sites between both mitochondrial membranes and require the electrical potential ΔΨ across the inner membrane. In the matrix, the presequences are proteolytically cleaved off. The proteins are then sorted to their functional destination and are assembled.

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References

  • Attardi G, Schatz (1988) Biogenesis of mitochondria. Ann Rev Cell Biol 4:289–333

    Article  PubMed  CAS  Google Scholar 

  • Chen W-J, Douglas MG (1987a) The role of protein structure in the mitochondrial import pathway. Unfolding of mitochondrially bound precursors is required for membrane translocation. J Biol Chem 262:15605–15609

    PubMed  CAS  Google Scholar 

  • Chen W-J, Douglas MG (1987b) Phosphodiester bond cleavage outside mitochondria is required for the completion of protein import into the mitochondrial matrix. Cell 49:651–658

    Article  PubMed  CAS  Google Scholar 

  • Chen W-J, Douglas MG (1988) An F1-ATPase β-subunit precursor lacking an internal tetramer-forming domain is imported into mitochondria in the absence of ATP. J Biol Chem 263:4997–5000

    PubMed  CAS  Google Scholar 

  • Cheng MY, Hartl F-U, Martin J et al. (1989) Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature (Lond) 337:620–625

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Eilers M, Schatz G (1986) Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature (Lond) 322:228–232

    Article  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 

  • Eilers M, Hwang S, Schatz G (1988) Unfolding and refolding of a purified precursor protein during import into isolated mitochondria. EMBO J 7:1139–1145

    PubMed  CAS  Google Scholar 

  • Ellis J (1987) Proteins as molecular chaperones. Nature (Lond) 328:378–379

    Article  CAS  Google Scholar 

  • Ellis RJ, Hemmingsen SM (1989) Molecular chaperones: proteins essential for the biogenesis of some macromolecular structures. Trends Biochem Sci 14:339–342

    Article  PubMed  CAS  Google Scholar 

  • Endo T, Schatz G (1988) Latent membrane perturbation activity of a mitochondrial precursor protein is exposed by unfolding. EMBO J 7:1153–1158

    PubMed  CAS  Google Scholar 

  • Flynn GC, Chappell TG, Rothman JE (1989) Peptide binding and release by proteins implicated as catalysts of protein assembly. Science 245:385–390

    Article  PubMed  CAS  Google Scholar 

  • Hartl F-U, Schmidt B, Weiss H, Wachter E, Neupert W (1986) Transport into mitochondria and intramitochondrial sorting of the Fe/S protein of ubiquinol cytochrome 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 

  • Hartl F-U, Pfanner N, Nicholson DW, Neupert W (1989) Mitochondrial protein import. Biochim Biophys Acta 988:1–45

    PubMed  CAS  Google Scholar 

  • Hemmingsen SM, Woolford C, van der Vies SM et al. (1988) Homologous plant and bacterial proteins chaperone oligomeric protein assembly. Nature (Lond) 333:330–334

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Kleene R, Pfanner N, Pfaller R et al. (1987) Mitochondrial porin of Neurospora crassa: cDNA cloning, in vitro expression and import into mitochondria. EMBO J 6:2627–2633

    PubMed  CAS  Google Scholar 

  • Mahlke K, Pfanner N, Martin J, Horwich AL, Hartl F-U, Neupert W (1990) Sorting pathways of mitochondrial inner membrane proteins. Eur J Biochem, in press

    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 

  • Ostermann J, Horwich AL, Neupert W, Hartl F-U (1989) Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis. Nature (Lond) 341:125–130

    Article  CAS  Google Scholar 

  • Pelham HRB (1986) Speculations on the functions of the major heat shock and glucose-regulated proteins. Cell 46:959–961

    Article  PubMed  CAS  Google Scholar 

  • Pfaller R, Freitag H, Harmey MA, Benz R, Neupert W (1985) A water-soluble form of porin from the mitochondrial outer membrane of Neurospora crassa: properties and relationship to the biosynthetic precursor form. J Biol Chem 260:8188–8193

    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) Biogenesis of mitochondrial energy transducing complexes. Curr Top Bioenerg 15:177–219

    CAS  Google Scholar 

  • Pfanner N, Neupert W (1989) Transport of proteins into mitochondria. Curr Opin Cell Biol 1: 624–629

    Article  PubMed  CAS  Google Scholar 

  • Pfanner N, Hartl F-U, Guiard B, Neupert W (1987a) Mitochondrial precursor proteins are imported through a hydrophilic membrane environment. Eur J Biochem 169:289–293

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Pfanner N, Hartl F-U, Neupert W (1988a) Import of proteins into mitochondria: a multi-step proeess. Eur J Biochem 175:205–212

    Article  PubMed  CAS  Google Scholar 

  • Pfanner N, Pfaller R, Kleene R, Ito M, Tropschug M, Neupert W (1988b) Role of ATP in mitochondrial protein import: conformational alteration of a precursor protein can substitute for ATP requirement. J Biol Chem 263:4049–4051

    PubMed  CAS  Google Scholar 

  • Pfanner N, Rassow J, Guiard B, Söllner T, Hartl F-U, Neupert W (1990) Energy requirements for unfolding and membrane translocation of precursor proteins during import into mitochondria. J Biol Chem, in press

    Google Scholar 

  • Randall SK, Shore GC (1989) Import of a mutant mitochondrial precursor fails to respond to stimulation by a cytosolic factor. FEBS Lett 250:561–564

    Article  PubMed  CAS  Google Scholar 

  • Rassow J, Guiard B, Wienhues U, Herzog V, Hartl F-U, Neupert W (1989) Translocation arrest by reversible folding of a precursor protein imported into mitochondria. A means to quantitate translocation contact sites. J Cell Biol 109:1421–1428

    Article  PubMed  CAS  Google Scholar 

  • Reading DS, Hallberg RL, Myers AM (1989) Characterization of the yeast HSP60 gene coding for a mitochondrial assembly factor. Nature (Lond) 337:655–659

    Article  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 

  • Schwaiger M, Herzog V, Neupert W (1987) Characterization of translocation contact sites involved in the import of mitochondrial proteins. J Cell Biol 105:235–246

    Article  PubMed  CAS  Google Scholar 

  • Veraer K, Schatz G (1987) Import of an incompletely folded precursor protein into isolated mitochondria requires an energized inner membrane, but no added ATP. EMBO J 6:2449–2456

    Google Scholar 

  • Zimmermann R, Sagstetter M, Lewis MJ, Pelham HRB (1988) Seventy-kilodalton heat shock proteins and additional component from reticulocyste lysate stimulate import of M13 procoat protein into microsomes. EMBO J 7:2875–2880

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Institut für Physiologische Chemie, Universität München, Goethestr. 33, D-8000, München 2, Germany

    Nikolaus Pfanner

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  1. Nikolaus Pfanner
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Editor information

Editors and Affiliations

  1. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, 63110, MO, USA

    Milton J. Schlesinger

  2. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Il Universitá degli Studi di Roma, I-00173, Roma, Italy

    M. Gabriella Santoro  & Enrico Garaci  & 

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© 1990 Springer-Verlag Berlin Heidelberg

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Pfanner, N. (1990). Mitochondrial Protein Import: Unfolding and Refolding of Precursor Proteins. In: Schlesinger, M.J., Santoro, M.G., Garaci, E. (eds) Stress Proteins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75815-7_6

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  • DOI: https://doi.org/10.1007/978-3-642-75815-7_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-75817-1

  • Online ISBN: 978-3-642-75815-7

  • eBook Packages: Springer Book Archive

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