Varied Responses of Central Nervous System Mitochondria to Calcium

  • Nickolay Brustovetsky
  • Janet M. Dubinsky


Liver Mitochondrion Mitochondrial Permeability Transition Mitochondrial Permeability Transition Pore Permeability Transition Pore Heart Mitochondrion 
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  1. Andreyev, A. Y., Mikhayloya, L. M., Starkov, A. A., and Kushnareva, Y., 1994, Ca[2+]-loading modulates potencies of cyclosporin A, Mg2+ and ADP to recouple permeabilized rat liver mitochondria, Biochem. Mol. Biol. Int. 34:367–373.PubMedGoogle Scholar
  2. Al-Nasser, I., and Crompton, M., 1986, The reversible Ca2+-induced permeabilization of rat liver mitochondria, Biochem J. 239(1):19–29.PubMedGoogle Scholar
  3. Andreyev, A. Y., Fahy, B., and Fiskum, G., 1998; Cytochrome c release from brain mitochondria is independent of the mitochondrial permeability transition, FEBS Lett. 439:373–376.CrossRefPubMedGoogle Scholar
  4. Ankarcrona, M., Dypbukt, J. M., Orrenius, S., and Nicotera, P., 1996, Calcineurin and mitochondrial function in glutamate-induced neuronal cell death, FEBS Lett. 394:321–324.CrossRefPubMedGoogle Scholar
  5. Bernardi., P., 1992, Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by the proton electrochemical gradient: Evidence that the pore can be opened by membrane depolarization, J. Biol. Chem. 267(13):8834–8839.PubMedGoogle Scholar
  6. Broekemeier, K. M., and Pfeiffer, D. R., 1995, Inhibition of the mitochondrial permeability transition by cyclosporin A during long time-frame experiments: Relationship between pore opening and the activity of mitochondrial phospholipases. Biochemistry 34:16440–16449.CrossRefPubMedGoogle Scholar
  7. Broekemeier, K. M., Schmid, P. C., Schmid, H. H. O., and Pfeiffer, D. R., 1985, Effect of phospholipase A2 inhibitors on ruthenium red-induced Ca2+ release from mitochondria, J. Biol. Chem 260:105–113.PubMedGoogle Scholar
  8. Broekemeier, K. M., Dempsey, M. E., and Pfeiffer, D. R., 1989, Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria, J. Biol. Chem 264:7826–7830.PubMedGoogle Scholar
  9. Broekemeier, K. M., Klocek, C. K.., and Pfeiffer, D. R., 1998, Proton selective substate of the mitochondrial permeability transition pore: Regulation by the redox state of the electron transport chain, Biochemistry 37: 13059–13065.CrossRefPubMedGoogle Scholar
  10. Brustovetsky, N. and Dubinsky, J. M., 1998a, Cyclosporin A inhibition of the permeability transition in brain depends upon mitochondrial potential, Soc. Neurosci. Abstr 24:1453.Google Scholar
  11. Brustovetsky, N., and Dubinsky, J. M., 1998b, Does the Ca2+ uniporter form the mitochondrial permeability transition pore? Biophys. J 74:A384.Google Scholar
  12. Buchanan, B. B., Eiermann, W., Riccio, P., Aquila, H., and Klingenberg, M., 1976, Antibody evidence for different conformational states of ADP, ATP translocator protein isolated from mitochondria, Proc. Natl. Acad. Sci. USA 73(7):2280–2284.PubMedGoogle Scholar
  13. Cassarino, D. S., Fall, C. P., Smith, T. S., and Bennett, J. P., 1998, Pramipexole reduces reactive oxygen species production in vivo and in vitro and inhibits the mitochondrial permeability transition produced by the parkinsonian neurotoxin methylpyridinium ion, J. Neurochem 71:295–301.PubMedGoogle Scholar
  14. Crompton, M., and Andreeva, L., 1994, On the interactions of Ca2+ and cyclosporin A with a mitochondrial inner membrane pore: A study using cobaltammine complex inhibitors of the Ca2+ uniporter, Biochem. J. 302:181–185.PubMedGoogle Scholar
  15. Crompton, M., Ellinger, H., and Costi, A., 1988, Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress, Biochem. J 255:357–360.PubMedGoogle Scholar
  16. Dubinsky, J. M., and Levi, Y., 1998, Calcium-induced activation of the mitochondrial permeability transition in hippocampal neurons, J. Neurosc. Res 53:728–741.Google Scholar
  17. Ellerby, H. M., Martin, S. J., Ellerby, L. M., Naiem, S. S., Rabizadeh, S., Salvesen, G. S., Casiano, C. A., Cashman, N. R., Green D. R., and Bredesen, D. E., 1997, Establishment of a cell-free system of neuronal apoptosis: Comparison of premitochondrial, mitochondrial, and postmitochondrial phases, J. Neurosci 17: 6165–6178.PubMedGoogle Scholar
  18. Eskes, R., Antonsson, B., Osensand, A., Montessuit, S., Richter, C., Sadoul, R., Mazzei, G., Nichols, A., and Martinou, J. C.. 1998, BAX-induced cytochrome c release from mitochondria is independent of the permeability transition pore but highly dependent on Mg2+ ions, J. Cell Biol 143:217–224.CrossRefPubMedGoogle Scholar
  19. Folbergrova, J., Li P. A., Uchino, H., Smith, M. L., and Siesjo, B. K., 1997, Changes in the bioenergetic state of rat hippocampus during 2.5 min of ischemia, and prevention of cell damage by cyclosporin A in hyperglycemic subjects, Exp Brain Res 114:44–50.PubMedGoogle Scholar
  20. Friberg, H., Ferrand-Drake, M., Bengtsson, F., Halestrap, A. P., and Wieloch, T., 1998a, Cyclosporin A, but not FK. 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death, J. Neurosci 18:5151–5159.PubMedGoogle Scholar
  21. Friberg, H., Ferrand-Drake, M., Boris-Moller, F., Halestrap, A. P., and Wieloch., T. 1998b, Differences in the activation of the mitochondrial permeability transition betweenbrain regions: Correlation to selective vulnerability, Soc. Neurosci. Abstr 24:1229.Google Scholar
  22. Green, D. R., and Reed, J. C., 1998, Mitochondria and apoptosis, Science 281:1309–1312.PubMedGoogle Scholar
  23. Gunter, T. E., Gunter, K. K., Sheu, S. S., and Gavin, C. E., 1994, Mitochondrial calcium transport: Physiological and pathological relevance. Am. J. Physiol 267:C313–C339.PubMedGoogle Scholar
  24. Halestrap, A. P., and Davidson, A. M., 1990, Inhibition of Ca2+-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase, Biochem. J 268:153–160.PubMedGoogle Scholar
  25. Hirsch, T., Susin, S. A., Marzo, I., Marchetti, P., Zamzami, N., and Kroemer, G., 1998, Mitochondrial permeability transition in apoptosis and necrosis, Cell Biol. Toxico 14:141–145.Google Scholar
  26. Ichas, F., Jouaville, L. S., and Mazat, J. P., 1997, Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals, Cell 89:1145–1153.CrossRefPubMedGoogle Scholar
  27. Keller, J. N., Guo, Q., Holtsberg, F. W., Brucekeller, A. J., and Mattson, M. P., 1998, Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and enhanced oxyradical production, J. Neurosci 18:4439–4450.PubMedGoogle Scholar
  28. Kristal, B. S., and Dubinsky, J. M., 1997, Mitochondrial permeability transition in the central nervous system: Induction by calcium-cycling dependent and independent pathways, J. Neurochem 69:524–538.PubMedGoogle Scholar
  29. Li, P. A., Uchino, H., Elmer, E.. and Siesjo, B. K., 1997, Amelioration by cyclosporin A of brain damage following 5 or 10min of ischemia in rats subjected to preischemic hyperglycemia, Brain Res 753:133–140.CrossRefPubMedGoogle Scholar
  30. Liu, X., Kim., O. N., Yang, J., Jemmerson, R., and Wang, X., 1996, Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c Cell 86:147–157.PubMedGoogle Scholar
  31. Murphy, A. N., Wang, G., and Richards, C. M., 1998, Further characterization of mitochondrial cytochrome c release and inhibition by BCL-2, Soc. Neurosci. Abstr 24:1945.Google Scholar
  32. Nicholls, D. G., and Ferguson, S. J., 1992, Bioenergetics 2 Academic, LondonGoogle Scholar
  33. Nieminen, A. L., Petrie, T. G., Lemasters, J. J., and Selman, W. R., 1996, Cyclosporin A delays mitochondrial depolarization induced by N-methyl-D-aspartate in cortical neurons: Evidence of the mitochondrial permeability transition, Neuroscience 75:993–997.PubMedGoogle Scholar
  34. Novgorodov, S. A., and Gudz, T. I., 1996, Permeability transition pore of the inner mitochondrial membrane can operate in two open states with different selectivities, J. Bioenerg. Biomembr 28:139–146.CrossRefPubMedGoogle Scholar
  35. Petronilli, V, Cola, C., and Bernardi, P., 1993, Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore: II. The minimal requirements for pore induction underscore a key role for transmembrane electrical potential, matrix pH, and matrix Ca2+, J. Biol. Chem 268:1011–1016.PubMedGoogle Scholar
  36. Savage, M. K., and Reed, D. J., 1994, Release of mitochondrial glutathione and calcium by a cyclosporin A-sensitive mechanism occurs without large amplitude swelling, Arch. Biochem., Biophys 315:142–152.CrossRefGoogle Scholar
  37. Schinder, A. F., Olson, E. C., Spitzer, N. C., and Montal, M., 1996, Mitochondrial dysfunction is a primary event in glutamate neurotoxicity, J. Neurosci 16:6125–6133.PubMedGoogle Scholar
  38. Skulachev, V P., 1996, Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants, Q. Rev. Biophys 29:169–202.PubMedGoogle Scholar
  39. White, R. J., and Reynolds, I. J., 1996, Mitochondrial depolarization in glutamate-stimulated neurons: An early signal specific to excitotoxin exposure, J. Neurosci 16:5688–5697.PubMedGoogle Scholar
  40. Zamzami, N. Susin, S. A., Marchetti, P., Hirsch, T., Gomez-Monterrey, I., Castedo, M., and Kroemer, G., 1996, Mitochondrial control of nuclear apoptosis, J. Exp. Med 183:1533–1544.CrossRefPubMedGoogle Scholar
  41. Zamzami, N., Brenner, C., Marzo, I., Susin, S. A., and Kroemer, G., 1998, Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins, Oncogene 16:2265–2282.PubMedGoogle Scholar
  42. Zoratti, M., and Szabò, I., 1995, The mitochondrial permeability transition, Biochim. Biophys. Acta 1241:139–176.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Nickolay Brustovetsky
    • 1
  • Janet M. Dubinsky
    • 2
  1. 1.Department of NeuroscienceUniversity of MinnesotaMinneapolis
  2. 2.Department of PhysiologyUniversity of MinnesotaMinneapolis

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