Journal of Bioenergetics and Biomembranes

, Volume 19, Issue 3, pp 297–303

Action of cyclosporine on mitochondrial calcium fluxes

  • N. Fournier
  • G. Ducet
  • A. Crevat
Research Articles


Cyclosporine (Cys A) is a potent immunosuppressor used to reduce rejection in transplantation surgery. We studied its action upon mitochondrial functions: oxidative phosphorylation and Ca2+ movements through mitochondrial membrane. We show that Cys A exhibits an inhibitory effect upon mitochondrial respiration. This result is in good agreement with previous works and may be correlated with Cys A toxicity. The action of cyclosporine on calcium fluxes is more pronounced. Indeed it blocks mitochondrial calcium efflux and allows mitochondria to accumulate a large amount of calcium. If this effect occurs in the cell, it would induce a Ca2+ decrease in cytosol. This action might be correlated with the inhibitory effect of Cys A upon the mitogenic stimulation of T lymphocytes.

Key Words

Cyclosporine calcium mitochondria 


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  1. Borel, J. F., Feurer, C., Magnee, C., and Stahelin, H. (1977). Effect of the new antilymphocyte peptide Cyclosporine A in animals,Immunology 32, 1017.Google Scholar
  2. Caine, R. Y. (1979). Immunosuppression for organ grafting. Observation on Cyclosporine A,Immunol. Rev. 46, 113.Google Scholar
  3. Chance, B., and William, G. R. (1956). The respiratory chain and oxidative phosphorylation,Adv. Enzymol. 17, 65.Google Scholar
  4. Ducet, G., Gidrol, X., and Richaud, P. (1983). Membrane potential changes in coupled potato mitochondria,Physiol. Veg. 21, 385.Google Scholar
  5. Ferrero, M. E., and Marni, A. (1985). The effect of Cyclosporine on nucleotide content of rat lymphocytes,Int. J. Immunopharmacol. 7, 897.Google Scholar
  6. Fiskum, G. (1984).Metal Ions in Biological Systems. Volume 17:Calcium and Its Role in Biology, Marcel Dekker, New York and Basel, p. 187.Google Scholar
  7. Hay, R., Tammi, K., Ryffel, B., and Mihatsch, M. J. (1986). Alterations in molecular structure of renal mitochondria associated with Cyclosporine A treatment,Clin. Nephrol. 25, Suppl. 1, S 23.Google Scholar
  8. Johnson, G., and Lardy, H. A. (1967). Isolation of liver or kidney mitochondria,Methods Enzymol. 10, 94.Google Scholar
  9. Jung, K., and Pergande, M. (1985). Influence of Cyclosporine A on the respiration of isolated rat kidney mitochondria,FEBS Lett. 183, 167.Google Scholar
  10. Kamo, N., Mutatsugu, M., Hongoh, R., and Kobatake, Y. (1979). Membrane potential of mitochondria measured with an electrode sensitive to tetraphenylphosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state,J. Membr. Biol. 49, 105.Google Scholar
  11. Kay, J. E., Benzie, C. R., and Borghetti, A. F. (1983). Effect of Cyclosporine A on lymphocyte activation by the calcium ionophore A 23187,Immunology 50, 441.Google Scholar
  12. Morris, P. J. (1981). Cyclosporine A,Transplantation 32, 349.Google Scholar
  13. Nicchitta, C. V., Kamoun, M., and Williamson, J. R. (1985). Cyclosporine augments receptor-mediated cellular Ca2+ fluxes in isolated hepatocytes,J. Biol. Chem. 260, 13613.Google Scholar
  14. Tsien, R. Y., Pozzan, T., and Rink, T. J. (1982). T cell mitogens cause early changes in cytoplasmic free Ca2+ membrane potential in lymphocytes,Nature (London)295, 68.Google Scholar
  15. Verpooten, G. A., Wybo, I., Pattyn, V. M., Hendrix, P. G., Giuliano, R. A., Nouwen, E. J., Roels, F., and de Broe, M. E. (1986). Cyclosporine nephrotoxicity: comparative cytochemical study of rat kidney and human allograft biopsies,Clin. Nephrol. 25, Suppl. 1, S 18.Google Scholar
  16. Wright, B., Greig, R., and Poste, G. (1984). Inhibition of macrophage activation and tumor cell cytolysis by Cyclosporine A,Biochem. Biophys. Res. Commun. 123, 710.Google Scholar

Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • N. Fournier
    • 1
  • G. Ducet
    • 2
  • A. Crevat
    • 1
  1. 1.Laboratoire de BiophysiqueFaculté de PharmacieMarseilleFrance
  2. 2.Laboratoire de Physiologie CellulaireFaculte des SciencesMarseilleFrance
  3. 3.Laboratoire de BiophysiqueFaculté de PharmacieMarseille Cedex 5France

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