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Mitochondrial Calcium Signaling Driven by the IP3 Receptor

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Abstract

Many agonists bring about their effects on cellular functions through a rise incytosolic [Ca2+]([Ca2+]c) mediated by the second messenger inositol 1,4,5-trisphosphate (IP3). Imaging studiesof single cells have demonstrated that [Ca2+]c signals display cell specific spatiotemporalorganization that is established by coordinated activation of IP3 receptor Ca2+ channels.Evidence emerges that cytosolic calcium signals elicited by activation of the IP3 receptors areefficiently transmitted to the mitochondria. An important function of mitochondrial calciumsignals is to activate the Ca2+-sensitive mitochondrial dehydrogenases, and thereby to meetdemands for increased energy in stimulated cells. Activation of the permeability transitionpore (PTP) by mitochondrial calcium signals may also be involved in the control of cell death.Furthermore, mitochondrial Ca2+ transport appears to modulate the spatiotemporal organizationof [Ca2+]c responses evoked by IP3 and so mitochondria may be important in cytosolic calciumsignaling as well. This paper summarizes recent research to elucidate the mechanisms andsignificance of IP3-dependent mitochondrial calcium signaling.

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References

  • Andreyev, A. Y., Fahy, B., and Fiskum, G. (1998). FEBS Lett. 439, 373-376.

    Google Scholar 

  • Babcock, D. F., and Hille, B. (1998). Current Opinions Neurobiol. 8, 398-404.

    Google Scholar 

  • Babcock, D. F., Herrington, J., Goodwin, P. C., Park, Y. B., and Hille, B. (1997). J. Cell Biol. 136, 833-44.

    Google Scholar 

  • Baffy, G., Miyashita, T., Williamson, J. R., and Reed, J. C. (1993). J. Biol. Chem. 268, 6511-6519.

    Google Scholar 

  • Balaban, R. S., Dennis, V. W., and Mandel, L. J. (1981). Amer. J. Physiol. 240, F337-42.

    Google Scholar 

  • Bernardi, P. (1996). Biochim. Biophys. Acta 1275, 5-9.

    Google Scholar 

  • Bernardi, P., and Petronilli, V. (1996). J. Bioenerg. Biomembr. 28, 131-8.

    Google Scholar 

  • Berridge, M. J. (1993). Nature (London) 361, 315-325.

    Google Scholar 

  • Berridge, M. J. (1997). Nature (London) 386, 759-760.

    Google Scholar 

  • Bootman, M. D., and Berridge, M. J. (1996). Current Biol. 6, 855-865.

    Google Scholar 

  • Bootman, M. D., Berridge, M. J., and Lipp, P. (1997). Cell 91, 367-373.

    Google Scholar 

  • Borst, J. G., and Sakmann, B. (1996). Nature (London) 383, 431-434.

    Google Scholar 

  • Budd, S. L., and Nicholls, D. G. (1996). J. Neurochem. 67, 2282-2291.

    Google Scholar 

  • Clapham, D. E. (1995). Cell 80, 259-268.

    Google Scholar 

  • Cobbold, P. H., and Cuthbertson, K. S. (1990). Seminars Cell Biol. 1, 311-321.

    Google Scholar 

  • Cooper, R. L., Winslow, J. L., Govind, C. K., and Atwood, H. L. (1996). J. Neurophysiol. 75, 2451-2466.

    Google Scholar 

  • Csordás, G., Thomas, A. P., and Hajnóczky, G. (1999). EMBO J. 18, 96-108.

    Google Scholar 

  • del Castillo, J., and Katz, B. (1954). J. Physiol. 124, 560-573.

    Google Scholar 

  • Denton, R. M., and McCormack, J. G. (1980). FEBS Lett. 119, 1-8.

    Google Scholar 

  • Di Lisa, F., Blank, P. S., Colonna, R., Gambassi, G., Silverman, H. S., Stern, M. D., and Hansford, R. G. (1995). J. Physiol. (London) 486, 1-13.

    Google Scholar 

  • Donnadieu, E., and Bourguignon, L. Y. (1996). Cell Calcium 1, 53-61.

    Google Scholar 

  • Duchen, M. R. (1992). Biochem. J. 283, 41-50.

    Google Scholar 

  • Duchen, M. R., Peuchen, S., and Nowicky, A. (1993). Biomedical. Res. 14 (Suppl. 2), 139-146.

    Google Scholar 

  • Dunlap, K., Luebke, J. I., and Turner, T. J. (1995). Trends Neurosci. 18, 89-98.

    Google Scholar 

  • Golovina, V. A., and Blaustein, M. P. (1997). Science 275, 1643-1648.

    Google Scholar 

  • Green, D., and Kroemer, G. (1998). Trends Cell Biol. 8, 267-271.

    Google Scholar 

  • Green, D. R., and Reed, J. C. (1998). Science 281, 1309-1312.

    Google Scholar 

  • Gunter, T. E., and Pfeiffer, D. R. (1990). Amer. J. Physiol. 258, C755-86.

    Google Scholar 

  • Gunter, T. E., Gunter, K. K., Sheu, S. S., and Gavin, C. E. (1994). Amer. J. Physiol. 267, C313-C339.

    Google Scholar 

  • Gunter, T. E., Buntinas, L., Sparagna, G. C., and Gunter, K. K. (1998). Biochim. Biophys. Acta 1366, 5-15.

    Google Scholar 

  • Hajnóczky, G., Robb-Gaspers, L. D., Seitz, M. B., and Thomas, A. P. (1995). Cell 82, 415-424.

    Google Scholar 

  • Hajnóczky, G., Hager, R., and Thomas, A. P. (1999). J. Biol. Chem. 274, 14157-62.

    Google Scholar 

  • Halestrap, A. P., and Davidson, A. M. (1990). Biochem. J. 268, 153-160.

    Google Scholar 

  • Hansford, R. G. (1980). Current Topics Bioenerg. 10, 217-277.

    Google Scholar 

  • Hehl, S., Golard, A., and Hille, B. (1996). Cell Calcium 20, 515-24.

    Google Scholar 

  • Hockenbery, D., Nunez, G., Milliman, C., Schreiber, R. D., and Korsmeyer, S. J. (1990). Nature (London) 348, 334-336.

    Google Scholar 

  • Hoek, J. B., Walajtys-Rode, E., and Wang, X. (1997). Mol. Cell Biochem. 174, 173-179.

    Google Scholar 

  • Hoth, M., Fanger, C. M., and Lewis, R. S. (1997). J. Cell Biol. 137, 633-648.

    Google Scholar 

  • Horne, J. H., and Meyer, T. (1997). Science 276, 1690-1693.

    Google Scholar 

  • Huser, J., Rechenmacher, C. E., and Blatter, L. A. (1998). Biophys. J. 74, 2129-37.

    Google Scholar 

  • Ichas, F., and Mazat, J. P. (1998). Biochim. Biophys. Acta 1366, 33-50.

    Google Scholar 

  • Ichas, F., Jouaville, L. S., and Mazat, J. P. (1997). Cell 89, 1145-1153.

    Google Scholar 

  • Ichas, F., Ouhabi, R., Sidash, S. S., and Mazat, J. P. (1999). Biophys. J. 76, A235.

    Google Scholar 

  • Jou, M. J., Peng, T. I., and Sheu, S. S. (1996). J. Physiol. (London) 497, 299-308.

    Google Scholar 

  • Jouaville, L. S., Ichas, F., Holmuhamedov, E. L., Camacho, P., and Lechleiter, J. D. (1995). Nature (London) 377, 438-441.

    Google Scholar 

  • Jouaville, L. S., Ichas, F., and Mazat J. P. (1998). Mol. Cell. Biochem. 184, 371-6.

    Google Scholar 

  • Katz, B. (1969). The Release of Neural Transmitter Substances, (Liverpool University Press), Liverpool.

    Google Scholar 

  • Kneen, M., Farinas, J., Li, Y., and Verkman, A. S. (1998). Biophys. J. 74, 1591-1599.

    Google Scholar 

  • Kroemer, G., Zamzami, N., and Susin, S. A. (1997). Immunol. Today 18:44-51.

    Google Scholar 

  • Kroemer, G., Dallaporta, B., and Resche-Rigon, M. (1998). Annu. Rev. Physiol. 60, 619-642.

    Google Scholar 

  • Kunz, W., and Bohme, G. (1969). Acta Biol. Med. Ger. 22, 643-51.

    Google Scholar 

  • Landolfi, B., Curci, S., Debellis, L., Pozzan, T., and Hofer, A. M. (1998). J. Cell Biol. 142, 1235-43.

    Google Scholar 

  • Lemasters, J. J., Nieminen, A. L., Qian, T., Trost, L. C., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner, D. A., and Herman, B. (1998). Biochim. Biophys. Acta 1366, 177-196.

    Google Scholar 

  • Li, H., Zhu, H., Xu, C. J., and Yuan, J. (1998). Cell 94, 491-501.

    Google Scholar 

  • Llopis, J., McCaffery, J. M., Miyawaki, A., Farquhar, M. G., and Tsien, R. Y. (1998). Proc. Natl. Acad. Sci. USA 95, 6803-6808.

    Google Scholar 

  • Loew, L. M., Tuft, R. A., Carrington, W., and Fay, F. S. (1993). Biophys. J. 65, 2396-2407.

    Google Scholar 

  • Loew, L. M., Carrington, W., Tuft, R. A., and Fay, F. S. (1994). Proc. Natl. Acad. Sci. USA 91, 12579-12583.

    Google Scholar 

  • Lopez-Lopez, J. R., Shacklock, P. S., Balke, C. W., and Wier, W. G. (1995). Science 268, 1042-1045.

    Google Scholar 

  • Lukacs, G. L., and Kapus, A. (1987). Biochem. J. 248, 609-613.

    Google Scholar 

  • Maeda, N., Niinobe, M., Inoue, Y., and Mikoshiba, K. (1989). Dev. Biol. 133, 67-76.

    Google Scholar 

  • Mannella, C. A., Buttle, K., Rath, B. K., and Marko, M. (1998). Biofactors 8, 225-8.

    Google Scholar 

  • Marzo, I., Brenner, C., Zamzami, N., Jurgensmeier, J. M., Susin, S. A., Vieira, H. L., Prevost, M. C., Xie, Z., Matsuyama, S., Reed, J. C., and Kroemer, G. (1998). Science 281, 2027-2031.

    Google Scholar 

  • McCormack, J. G., Halestrap, A. P., and Denton, R. M. (1990). Physiol. Rev. 70, 391-425.

    Google Scholar 

  • Mignery, G. A., Sudhof, T. C., Takei, K., and De Camilli, P. (1989). Nature (London) 342, 192-195.

    Google Scholar 

  • Murphy, A. N., Bredesen, D. E., Cortopassi, G., Wang, E., and Fiskum, G. (1996). Proc. Natl. Acad. Sci. USA 93, 9893-9898.

    Google Scholar 

  • Nicholls, D. G., and Budd, S. L. (1998a). Biochim. Biophys. Acta 1366, 97-112.

    Google Scholar 

  • Nicholls, D. G., and Budd, S. L. (1998b). Biofactors 8, 287-299.

    Google Scholar 

  • Oltvai, Z. N., Milliman, C. L., and Korsmeyer, S. J. (1993). Cell 74, 609-619.

    Google Scholar 

  • Parker, I., and Yao, Y. (1996). J. Physiol. (London) 491, 663-668.

    Google Scholar 

  • Parker, I., Choi, J., and Yao, Y. (1996). Cell Calcium 20, 105-121.

    Google Scholar 

  • Pastorino, J. G., Chen, S. T., Tafani, M., Snyder, J. W., and Farber, J. L. (1998). J. Biol. Chem. 273, 7770-7775.

    Google Scholar 

  • Petersen, O. H., Petersen, C. C., and Kasai, H. (1994). Annu. Rev. Physiol. 56, 297-319.

    Google Scholar 

  • Petit, P. X., Goubern, M., Diolez, P., Susin, S. A., Zamzami, N., and Kroemer, G. (1998). FEBS Lett. 426, 111-116.

    Google Scholar 

  • Pozzan, T., Rizzuto, R., Volpe, P., and Meldolesi, J. (1994). Physiol. Rev. 74, 595-636.

    Google Scholar 

  • Pralong, W. F., Hunyady, L., Varnai, P., Wollheim, C. B., and Spät, A. (1992). Proc. Natl. Acad Sci. USA 89, 132-136.

    Google Scholar 

  • Pralong, W. F., Spät, A., and Wollheim, C. B. (1994). J. Biol. Chem. 269, 27310-27314.

    Google Scholar 

  • Prentki, M., Glennon, M. C., Thomas, A. P., Morris, R. L., Matschinsky, F. M., and Corkey, B. E. (1988). J. Biol. Chem. 263, 11044-11047.

    Google Scholar 

  • Putney, J. W. Jr. (1998). Science 279, 191-192.

    Google Scholar 

  • Reber, B. F. X., and Schindelholz, B. (1996). Pflugers Arch. 432, 893-903.

    Google Scholar 

  • Reed, J. C. (1997). Cell 91, 559-562.

    Google Scholar 

  • Ricken, S., Leipziger, J., Greger, R., and Nitschke, R. J. (1998). Biol. Chem. 273, 34961-34969.

    Google Scholar 

  • Rizzuto, R., Brini, M., Murgia, M., and Pozzan, T. (1993). Science 262, 744-747.

    Google Scholar 

  • Rizzuto, R., Bastianutto, C., Brini, M., Murgia, M., and Pozzan, T. (1994). J. Cell Biol. 126, 1183-1194.

    Google Scholar 

  • Rizzuto, R., Brini, M., Pizzo, P., Murgia, M., and Pozzan, T. (1995). Current Biol. 5, 635-642.

    Google Scholar 

  • Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., and Pozzan, T. (1998). Science 280, 1763-1766.

    Google Scholar 

  • Robb-Gaspers, L. D., Rutter, G. A., Burnett, P., Hajnóczky, G., Denton, R. M., and Thomas, A. P. (1998a). Biochim. Biophys. Acta 1366, 17-32.

    Google Scholar 

  • Robb-Gaspers, L. D., Burnett, P., Rutter, G. A., Denton, R. M., Rizzuto, R., and Thomas, A. P. (1998b). EMBO J. 17, 4987-5000.

    Google Scholar 

  • Rohacs, T., Nagy, G., and Spät, A. (1997). Biochem. J. 322, 785-92.

    Google Scholar 

  • Rutter, G. A., Burnett, P., Rizzuto, R., Brini, M., Murgia, M., Pozzan, T., Tavare, J. M, and Denton, R. M. (1996). Proc. Natl. Acad. Sci. USA 93, 5489-5494.

    Google Scholar 

  • Satoh, T., Ross, C. A., Villa, A., Supattapone, S., Pozzan, T., Snyder, S. H., and Meldolesi, J. (1990). J. Cell Biol. 111, 615-624.

    Google Scholar 

  • Scholz, R., Thurman, R. G., Williamson, J. R., Chance, B., and Bucher, T. J. (1969). Biol. Chem. 244, 2317-2324.

    Google Scholar 

  • Shore, G. C. and Tata, J. R. (1977). J. Cell Biol. 72, 714-725.

    Google Scholar 

  • Simpson, P. B., and Russell, J. T. (1996). J. Biol. Chem. 271, 33493-33501.

    Google Scholar 

  • Simpson, P. B., Mehotra, S., Lange, G. D., and Russell J. T. (1997). J. Biol. Chem. 272, 22654-22661.

    Google Scholar 

  • Skulachev, V. P. (1998). FEBS Lett. 423, 275-280.

    Google Scholar 

  • Sparagna, G. C., Gunter, K. K., Sheu, S. S., and Gunter, T. E. (1995). J. Biol. Chem. 270, 27510-27515.

    Google Scholar 

  • Thomas, A. P., Renard, D. C., and Rooney, T. A. (1991). Cell Calcium 12, 111-26.

    Google Scholar 

  • Thomas, A. P., Bird, G. S, Hajnóczky, G., Robb-Gaspers, L. D., and Putney, J. W. Jr. (1996). FASEB J. 10, 1505-1517.

    Google Scholar 

  • Tsien, Y. T., and Bacskai, B. J. (1995). In Handbook of Confocal Microscopy (Pawley, J. B. ed.), Plenum Press, New York, pp. 459-478.

    Google Scholar 

  • Yang, J. C., and Cortopassi, G. A. (1998). Free Radicals Biol. Med. 24, 624-631.

    Google Scholar 

  • Yao, Y., Choi, J., and Parker, I. (1995). J. Physiol. (London) 482, 533-553.

    Google Scholar 

  • Zoratti, M., and Szabo, I. (1995). Biochim. Biophys. Acta 1241, 139-76.

    Google Scholar 

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Hajnóczky, G., Csordás, G., Krishnamurthy, R. et al. Mitochondrial Calcium Signaling Driven by the IP3 Receptor. J Bioenerg Biomembr 32, 15–25 (2000). https://doi.org/10.1023/A:1005504210587

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