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Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria

Nature volume 322, pages 228–232 (1986)Cite this article

Abstract

Methotrexate, a folate antagonist, blocks import into mitochondria of mouse dihydrofolate reductase fused to a mitochondrial presequence. Methotrexate does not mask the presequence, but stabilizes the dihydrofolate reductase moiety. It does not inhibit import of the authentic precursor from which the presequence is derived. This suggests that dihydrofolate reductase must at least partly unfold in order to be transported across mitochondrial membranes.

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References

  1. Wickner, W. T. & Lodish, H. F. Science 230, 400–407 (1985).

    ADS  CAS  Article  Google Scholar 

  2. Blobel, G. & Dobberstein, B. J. Cell Biol. 67, 835–851 (1975).

    CAS  Article  Google Scholar 

  3. Randall, L. L. & Hardy, S. J. S. in Modern Cell Biology Vol. 3, 1–20 (Liss, New York, 1984).

    Google Scholar 

  4. Cullis, P. R. & De Kruijff, B. Biochim. biophys. Acta 559, 399–420 (1979).

    CAS  Article  Google Scholar 

  5. Hurt, E. C., Pesold-Hurt, B. & Schatz, G. FEBS Lett. 178, 306–310 (1984).

    CAS  Article  Google Scholar 

  6. Hurt, E. C., Pesold-Hurt, B., Suda, K., Oppliger, W. & Schatz, G. EMBO J. 4, 2061–2068 (1985).

    CAS  Article  Google Scholar 

  7. Chang, A. C. Y. et al. Nature 275, 617–624 (1978).

    ADS  CAS  Article  Google Scholar 

  8. Kaufman, B. T. & Pierce, J. V. Biochem. biophys. Res. Commun. 44, 608–613 (1971).

    CAS  Article  Google Scholar 

  9. Volz, K. W. et al. J. biol. Chem. 257, 2528–2536 (1982).

    CAS  PubMed  Google Scholar 

  10. Castaldo, R. A., Gump, D. W. & McCormack, J. J. Antimicrob. Ag. Chemother. 15, 81–86 (1979).

    CAS  Article  Google Scholar 

  11. Maarse, A. C. et al. EMBO J. 3, 2831–2837 (1984).

    CAS  Article  Google Scholar 

  12. Young, E. T. & Pilgrim, D. B. Molec. Cell. Biol. 5, 3024–3034 (1985).

    CAS  Article  Google Scholar 

  13. Van Loon, A. P. G. M., Brändli, A. & Schatz, G. Cell 44, 801–812 (1986).

    CAS  Article  Google Scholar 

  14. Hurt, E. C., Pesold-Hurt, B. & Schatz, G. EMBO J. 3, 3149–3156 (1984).

    CAS  Article  Google Scholar 

  15. Böhni, P. C., Daum, G. & Schatz, G. J. biol. Chem. 258, 4937–4943 (1983).

    PubMed  Google Scholar 

  16. Matthews, D. A. et al. J. biol. Chem. 260, 381–391 (1985).

    CAS  PubMed  Google Scholar 

  17. Kumar, A. A., Blankenship, D. T., Kaufman, B. T. & Freisheim, J. H. Biochemistry 19, 667–678 (1980).

    CAS  Article  Google Scholar 

  18. Stone, D. & Phillips, A. W. FEBS Lett. 74, 85–87 (1977).

    CAS  Article  Google Scholar 

  19. Schleyer, M. & Neupert, W. Cell 43, 339–350 (1985).

    CAS  Article  Google Scholar 

  20. Dretzen, G., Bellard, M., Sassone-Corsi, P. & Chambon, P. Analyt. Biochem. 112, 295–298 (1981).

    CAS  Article  Google Scholar 

  21. Amann, E., Brosius, J. & Ptashne, M. Gene 25, 167–178 (1983).

    CAS  Article  Google Scholar 

  22. Bolivar, F. & Backman, K. Meth. Enzym. 68, 245–268 (1979).

    CAS  Article  Google Scholar 

  23. Stanley, K. K. Nucleic Acids Res. 11, 4077–4092 (1983).

    CAS  Article  Google Scholar 

  24. Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1982).

    Google Scholar 

  25. Neu, H. C. & Heppel, L. A. J. biol. Chem. 240, 3685–3692 (1965).

    CAS  Google Scholar 

  26. Gupta, S. V. et al. Biochemistry 16, 3073–3079 (1977).

    CAS  Article  Google Scholar 

  27. Wray, W., Boulikas, T., Wray, V. P. & Hancock, R. Analyt. Biochem. 118, 197–203 (1981).

    CAS  Article  Google Scholar 

  28. Van Loon, A. P. G. M., Maarse, A. C., Riezman, H. & Grivell, L. A. Gene 26, 261–272 (1983).

    CAS  Article  Google Scholar 

  29. Gasser, S. M., Daum, G. & Schatz, G. J. biol. Chem. 257, 13034–13041 (1982).

    CAS  PubMed  Google Scholar 

Download references

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Affiliations

  1. Biocenter, University of Basel, CH-4056, Basel, Switzerland

    Martin Eilers & Gottfried Schatz

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  1. Martin Eilers
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  2. Gottfried Schatz
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Eilers, M., Schatz, G. Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature 322, 228–232 (1986). https://doi.org/10.1038/322228a0

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  • DOI: https://doi.org/10.1038/322228a0

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