Skip to main content
SpringerLink
Log in

Molecular Chaperones and Mitochondrial Protein Folding

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

Precursor proteins destined for the mitochondrial matrix traverse inner and outer organelle membranes in an extended conformation. Translocation events are therefore integrally coupled to the processes of protein unfolding in the cytosol and protein refolding in the matrix. To successfully import proteins from the cytoplasm into mitochondria, cells have recruited a variety of molecular chaperone systems and folding catalysts. Within the organelles, mitochondrial Hsp70 (mt-Hsp70) is a major player in this process and exerts multiple functions. First, mt-Hsp70 binds together with cohort proteins to incoming polypeptide chains, thus conferring unidirectionality on the translocation process, and then assists in their refolding. A subset of imported proteins requires additional assistance by chaperonins of the Hsp60/Hsp10 family. Protein folding occurs within the cavity of these cylindrical complexes. A productive interaction of precursor proteins with molecular chaperones in the matrix is not only crucial for correct refolding and assembly, but also for processing of presequences, intramitochondrial sorting, and degradation of proteins. This review focuses on the role of mt-Hsp70 and Hsp60/Hsp10 in protein folding in the mitochondrial matrix and discusses recent findings on their molecular mechanism of action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Blond-Elguindi, S., Cwirla, S. E., Dower W. J., Lipshutz, R. J., Sprang, S. R., Sambrook, J. F., and Gething, M. J. (1993). Cell 75, 717–729.

    Google Scholar 

  • Bolliger, L., Deloche, O., Glick, B. S., Georgopoulos, C., Jenö, P., Kronidou, N., Horst, M., Morishima, N., and Schatz, G. (1994). EMBO J. 13, 1998–2006.

    Google Scholar 

  • Braig, K., Otwinowski, Z., Hegde, R., Boisvert, D. C., Joachimiak, A., Horwich A. L., and Sigler, P. B. (1994). Nature 371, 578–586.

    Google Scholar 

  • Braun, H. P., Emmermann, M., Kruft, V., and Schmitz, U. K. (1992). EMBO J. 11, 3219–3227.

    Google Scholar 

  • Cheng, M. Y., Hartl, F.-U., Martin, J., Pollock, R. A., Kalousek, F., Neupert, W., Hallberg, E. M., Hallberg, R. L., and Horwich, A. L. (1989). Nature 337, 620–625.

    Google Scholar 

  • Cyr, D. M., Langer, T., and Douglas, M. G. (1994). Trends Biochem. Sci. 19, 176–181.

    Google Scholar 

  • Davis, E. S., Becker, A., Heitman, J., Hall, M. N., and Brennan, M. B. (1992). Proc. Natl. Acad. Sci. USA 89, 11169–11173.

    Google Scholar 

  • Gaitanaris, G. A., Vysokanov, A., Hung, G.-C., Gottesman, M. E., and Gragerov, A. (1994). Mol. Microbiol. 14, 861–869.

    Google Scholar 

  • Hartl, F. U., and Martin, J. (1995). Curr. Opin. Struct. Biol. 5, 92–102.

    Google Scholar 

  • Höhfeld, J., and Hartl, F. U. (1994). J. Cell Biol. 126, 305–315.

    Google Scholar 

  • Huckriede, A., and Agsteribbe, E. (1994). Biochim. Biophys. Acta 1227, 200–206.

    Google Scholar 

  • Hunt, J. F., Weaver, A. J., Landry, S. J., Gierasch, L., and Deisenhofer, J. (1996). Nature 379, 37–45.

    Google Scholar 

  • Ikeda, E., Yoshida, S., Mitsuzawa, H., Uno, I., and Toh-e, A. (1994). FEBS Lett. 339, 265–268.

    Google Scholar 

  • Isaya, G., Kalousek, F., and Rosenberg, L. E. (1992). Proc. Natl. Acad. Sci. USA 89, 8317–8321.

    Google Scholar 

  • Itoh, H., Kobayashi, R., Wakui, H., Komatsuda, A., Ohtani, H., Miura, A. B., Otaka, M., Masamune, O., Andoh, H., and Koyama, K. (1995). J. Biol. Chem. 270, 13429–13435.

    Google Scholar 

  • Kandror, O., Busconi, L., Sherman, M., and Goldberg, A. L. (1994). J. Biol. Chem. 269, 23575–23582.

    Google Scholar 

  • Kang, P.-J., Ostermann, J., Shilling, J., NeUpert, W., Craig, E. A., and Pfanner, N. (1990). Nature 348, 137–143.

    Google Scholar 

  • Kudlicki, W., Odom, O. W., Kramer, G., and Hardesty, B. (1994). J. Biol. Chem. 269, 16549–16553.

    Google Scholar 

  • Laloraya, S., Gambill, B. D., and Craig, E. A. (1994). Proc. Natl. Acad. Sci. USA 91, 6481–6485.

    Google Scholar 

  • Langer, T., Lu, C., Echols, H., Flanagan, J., Hauer, M. K., and Hartl, F.-U. (1992a) Nature 356, 683–689.

    Google Scholar 

  • Langer, T., Pfeifer, G., Martin, J., Baumeister, W., and Hartl F. U. (1992b). EMBO J. 11, 4757–4765.

    Google Scholar 

  • Leonhardt, S. A., Fearson, K., Danese, P. N., and Mason, T. L. (1993). Mol. Cell. Biol. 13, 6304–6313.

    Google Scholar 

  • Maarse, A. C., Blom, J., Grivell, L. A., and Meijer, M. (1992). EMBO J. 11, 3619–3628.

    Google Scholar 

  • Manning-Krieg, U. C., Scherer, P. E., and Schatz, G. (1991). EMBO J. 10, 3273–3280.

    Google Scholar 

  • Martin, J., Langer, T., Boteva, R., Schramel, A., Horwich, A. L., and Hartl, F. U. (1991). Nature 352, 36–42.

    Google Scholar 

  • Martin, J., Horwich, A. L., and Hartl, F.-U. (1992). Science 258, 995–998.

    Google Scholar 

  • Martin, J., Mayhew, M., Langer, T., and Hartl, F. U. (1993). Nature 366, 228–233.

    Google Scholar 

  • Matouschek, A., Rospert, S., Schmid, K., Glick, B. S., and Schatz, G. (1995). Proc. Natl. Acad. Sci. USA 92, 6319–6323.

    Google Scholar 

  • Mayhew, M., Da Silva, A. C. R., Martin, J., Erdjument-Bromage, H., Tempst, P., and Hartl, F. U. (1996). Nature 379, 420–426.

    Google Scholar 

  • Moczko, M., Schonfisch, B., Voos, W., Pfanner, N., and Rassow, J. (1995). J. Mol. Biol. 254, 538–543.

    Google Scholar 

  • Ostermann, J., Horwich, A. L., Neupert, W., and Hartl, F.-U. (1989). Nature 341, 125–130.

    Google Scholar 

  • Pollock, R. A., Hartl, F. U., Cheng, M. Y., Ostermann, J., Horwich, A. L., and Neupert, W. (1988). EMBO J. 7, 3493–3500.

    Google Scholar 

  • Rassow, J., Maarse, A. C., Krainer, E., Kübrich, M., Müller, H., Meijer, M, Craig, E. A., and Pfanner, N. (1994). J. Cell Biol. 127, 1547–1556.

    Google Scholar 

  • Rassow, J., Mohrs, K., Koidl, S., Barthelmess, I. B., Pfanner, N., and Tropschug, M. (1995). Mol. Cell. Biol. 15, 2654–2662.

    Google Scholar 

  • Rospert, S., Glick, B. S., Jenö, P., Schatz, G., Todd, M. J., Lorimer, G. H., and Viitanen, P. V. (1993a). Proc. Natl. Acad. Sci. USA 90, 10967–10971.

    Google Scholar 

  • Rospert, S., Junne, T., Glick, B. S., and Schatz, G. (1993b). FEBS Lett. 335, 358–360.

    Google Scholar 

  • Rospert, S., Looser, R., Dubaquié, Y., Matouschek, A., Glick, B. S., and Schatz, G. (1996). EMBO J. 15, 764–774.

    Google Scholar 

  • Rowley, N., Prip-Buus, C., Westermann, B., Brown, C., Schwarz, E., Barrell, B., and Neupert, W. (1994). Cell 77, 249–259.

    Google Scholar 

  • Saijo, T., Welch, W. J., and Tanaka, K. (1994). J. Biol. Chem. 269, 4401–4408.

    Google Scholar 

  • Scherer, P. E., Manning-Krieg, U. C., Jenö, P., Schatz, G., and Horst, M. (1992). Proc. Natl. Acad. Sci. USA 89, 11930–11934.

    Google Scholar 

  • Schmitt, M., Neupert, W., and Langer, T. (1995). EMBO J. 14, 3434–3444.

    Google Scholar 

  • Schneider, H.-C., Berthold, J., Bauer, M. F., Dietmeier, K., Guiard, B., Brunner, M., and Neupert, W. (1994). Nature 371, 768–774.

    Google Scholar 

  • Sherman, M. Y., and Goldberg, A. L. (1991). J. Bacteriol. 173, 7249–7256.

    Google Scholar 

  • Stoller, G., Rücknagel, K. P., Nierhaus, K. H., Schmid, F. X., Fischer, G., and Rahfeld, J.-U. (1995). EMBO J. 14, 4939–4948.

    Google Scholar 

  • Suzuki, C. K., Suda, K., Wang, N., and Schatz, G. (1994). Science 264, 273–276.

    Google Scholar 

  • Szabo, A., Langer, T., Schröder, H., Flanagan, J., Bukau, B., and Hartl, F. U. (1994). Proc. Natl. Acad. Sci. USA 91, 10345–10349.

    Google Scholar 

  • Ungermann, C., Guiard, B., Neupert, W., and Cyr, D. M. (1996). EMBO J. 15, 735–744.

    Google Scholar 

  • Van Dyck, L., Pearce, D. A., and Sherman, F. (1994). J. Biol. Chem. 269, 238–242.

    Google Scholar 

  • Wagner, I., Arlt, H., Van Dyck, L., Langer, T., and Neupert, W. (1994). EMBO J. 13, 5135–5145.

    Google Scholar 

  • Weissman, J. S., Kashi, Y., Fenton, W. A., and Horwich, A. L. (1994). Cell 78, 693–702.

    Google Scholar 

  • Westermann, B., Prip-Buus, C., Neupert, W., and Schwarz, E. (1995). EMBO J. 14, 3452–3460.

    Google Scholar 

  • Yang, M., Jensen, R. E., Yaffe, M. P., Oppliger, W., and Schatz, G. (1988). EMBO J. 7, 3857–3862.

    Google Scholar 

  • Zimmerman, S. B., and Trach, S. O. (1991). J. Mol. Biol. 222, 599–620.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Box G-J2, Providence, Rhode Island, 02912

    Jörg Martin

Authors
  1. Jörg Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, J. Molecular Chaperones and Mitochondrial Protein Folding. J Bioenerg Biomembr 29, 35–43 (1997). https://doi.org/10.1023/A:1022407705182

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022407705182

Search

Navigation