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The mitochondrial benzodiazepine receptor: Evidence for association with the voltage-dependent anion channel (VDAC)

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Abstract

Specific, high-affinity receptors for numerous drugs have recently been localized to mitochondrial membrane proteins. This review discusses the association of the mitochondrial receptor for benzodiazepines (mBzR) with the voltage-dependent anion channel (VDAC), indicating a possible auxiliary role for VDAC as a putative drug binding protein. The proposed subunit composition of the purified mBzR complex isolated from rat kidney mitochondria includes VDAC, which functions as a recognition site for benzodiazepines (e.g., flunitrazepam), the adenine nucleotide carrier (ADC), and an 18 kDa outer membrane protein identified by covalent labelling with the mBzR antagonists isoquinoline carboxamides (e.g., PK 14105).

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References

  • Anholt, R. R. H., Murphy, K. M. M., Mack, G. E., and Snyder, S. H. (1984).J. Neurosci. 4, 593–603.

    Google Scholar 

  • Anholt, R. R. H., Pedersen, P. L., DeSouza, E. B., and Snyder, S. H. (1986).J. Biol. Chem. 261, 576–586.

    Google Scholar 

  • Antkiewicz-Michaluk, L., Mukhin, A. G., Guidotti, A. A., and Krueger, K. E. (1988).J. Biol. Chem. 263, 17317–17321.

    Google Scholar 

  • Aurora, K. K., and Pedersen, P. L. (1988).J. Biol. Chem. 262, 17422–17428.

    Google Scholar 

  • Awad, M., and Gavish, M. (1987).J. Neurochem. 49, 1407–1414.

    Google Scholar 

  • Baker, M. E., and Fanestil, D. D. (1991).Cell 65, 721–722.

    Google Scholar 

  • Ballesta, J. J., Garcia, A. G., Gutierrez, L. M., Hildago, M. J., Palmero, M., Reig, J. A., and Viniegra, S. (1990).Br. J. Pharmacol. 101, 21–26.

    Google Scholar 

  • Basile, A. S., and Skolnick, P. (1986).J. Neurochem. 46, 305–308.

    Google Scholar 

  • Belleman, P., Ferry, D. R., Lubbecke, F., and Glossmann, H. (1981).Arzneimforsch./Drug Res. 31, 2064–2067.

    Google Scholar 

  • Benz, R., Wojtczak, L., Bosch, W., and Brdiczka, D. (1988).FEBS Lett. 231, 75–80.

    Google Scholar 

  • Braestrup, C., and Squires, R. F. (1977).Proc. Natl. Acad. Sci. USA 74, 3805–3809.

    Google Scholar 

  • Capponi, A. M., Rossier, M. F., Davies, E., and Vallotton, M. B. (1988).J. Biol. Chem. 263, 16113–16117.

    Google Scholar 

  • Colombini, M. (1980).Ann. New York Acad. Sci. 341, 552–563.

    Google Scholar 

  • Colombini, M., Yeung, C. L., Tung, J., and Konig, T. (1987).Biochim. Biophys. Acta 905, 270–286.

    Google Scholar 

  • Crompton, M., Ellinger, H., and Costi, A. (1988).Biochem. J. 255, 357–360.

    Google Scholar 

  • Cuatrecasas, P., and Hollenberg, M. (1976).Adv. Protein Chem. 30, 251–445.

    Google Scholar 

  • Curran, T., and Morgan, J. I. (1985).Science 229, 1265–1268.

    Google Scholar 

  • Curtis, B. M., and Catterall, W. A. (1985).Proc. Natl. Acad. Sci. USA 82, 2528–2532.

    Google Scholar 

  • De Pinto, V., Tommasino, M., Benz, R., and Palmieri, F. (1985).Biochim. Biophys. Acta 813, 230–242.

    Google Scholar 

  • De Pinto, V., Benz, R., and Palmieri, F. (1989).Eur. J. Biochem. 183, 179–187.

    Google Scholar 

  • De Souza, E. B., Anholt, R. R. H., Murphy, K. M. M., Snyder, S. H., and Kuhar, M. J. (1985).Endocrinology 116, 567–573.

    Google Scholar 

  • Doble, A., Burgevin, M. C., Menager, J., Ferris, O., Begassat, F., Renault, C., Dubroeucq, M. C., Gueremy, C., Uzan, A., and Le Fur, G. (1987a).J. Receptor Res. 7, 55–70.

    Google Scholar 

  • Doble, A., Ferris, O., Burgevin, M. C., Menager, J., Uzan, A., Dubroeucq, M. C., Renault, C., Gueremy, C., and Le Fur, G. (1987b).Mol. Pharmacol. 31, 42–49.

    Google Scholar 

  • Felgner, P. L., Messer, J. L., and Wilson, J. E. (1979).J. Biol. Chem. 254, 4946–4949.

    Google Scholar 

  • Ferry, D. R., Rombush, M., Goll, A., and Glossmann, H. (1984).FEBS Lett. 169, 112–118.

    Google Scholar 

  • Font, B., Eichenberger, D., Goldschmidt, D., and Vail, C. (1987).Mol. Cell Biochem. 78, 131–140.

    Google Scholar 

  • Handschumacher, R. E., Harding, M. W., Rice, J., and Drugge, R. J. (1984).Science 226, 544–547.

    Google Scholar 

  • Harding, M. W., and Handschumacher, R. E. (1988).Transplantation 46, 29S-35S.

    Google Scholar 

  • Hirsch, J. D., Beyer, C. F., Malkowitz, L., Beer, B., and Blume, A. J. (1989a).Mol. Pharmacol. 34, 157–163.

    Google Scholar 

  • Hirsch, J. D., Beyer, C. F., Malkowitz, L., Loullis, C. C., and Blume, A. J. (1989b).Mol. Pharmacol. 34, 164–172.

    Google Scholar 

  • Koritz, S. B. (1986).J. Steroid Biochem. 24, 569–576.

    Google Scholar 

  • Kottke, M., Adam, V., Riesinger, I., Bremm, G., Bosch, W., Brdiczka, D., Sandri, G., and Panfili, E. (1988).Biochim. Biophys. Acta 935, 87–102.

    Google Scholar 

  • Krueger, K. E. (1991).Neuropsychopharmacology 4, 237–244.

    Google Scholar 

  • Krueger, K. E., and Papadopoulos, V. (1990).J. Biol. Chem. 265, 15015–15022.

    Google Scholar 

  • Larcher, J-C., Vayssiere, J-L., Le Marguer, F. J., Cordeau, L. R., Keane, P. E., Bachy, A., Gros, F., and Croizat, B. P. (1989).Eur. J. Pharmacol. 161, 197–202.

    Google Scholar 

  • Lueddens, H. W. M., Newman, A. H., Rice, K. C., and Skolnick, P. (1986).Mol. Pharmacol. 29, 540–545.

    Google Scholar 

  • Mamalaki, C., Stephenson, F. A., and Barnard, E. A. (1987).EMBO J. 6, 561–565.

    Google Scholar 

  • McCabe, R. T., Schenheimer, J. A., Skolnick, P., Newman, A. H., Rice, K. C., Reig, J-A., and Klein, D. C. (1989).FEBS Let. 244, 262–267.

    Google Scholar 

  • McEnery, M. W., and Pedersen, P. L. (1986).J. Biol. Chem. 261, 1745–1752.

    Google Scholar 

  • McEnery, M. W., Hullihen, J. M., and Pedersen, P. L. (1989a).J. Biol. Chem. 264, 12029–12036.

    Google Scholar 

  • McEnery, M. W., Snowman, A. M., and Snyder, S. H. (1989b).Neurosci. Abstr. 15, 642.

    Google Scholar 

  • McEnery, M. W., Snowman, A. M., and Snyder, S. H., (1990).FASEB J. 45, 330a.

    Google Scholar 

  • McEnery, M. W., Snowman, A. M., Thompson, E. E., and Snyder, S. H. (1991a).Biophys. J. 59, 200a.

    Google Scholar 

  • McEnery, M. W., Snowman, A. M., Trifiletti, R. R., and Snyder, S. H. (1991b).Proc. Natl. Acad. Sci. USA, in press.

  • Mestre, M., Carriot, T., Berlin, C., Uzan, A., Renault, C., Dubroeucq, M. C., Gueremy, C., Doble, A. A., and Le Fur, G. (1984).Life Sci. 35, 953–962.

    Google Scholar 

  • Mohler, H., and Okada, T. (1977).Science 198, 849–851.

    Google Scholar 

  • Moreno-Sanchez, R., Hogue, B. A., Bravo, C., Newman, A. H., Basile, A. S., and Chiang, P. K. (1991a).Biochem. Pharmacol. 41, 1479–1484.

    Google Scholar 

  • Moreno-Sanchez, R., Bravo, C., Gutierrez, J., Newman, A. H., and Chaing, P. K. (1991b).Int. J. Biochem. 23, 207–213.

    Google Scholar 

  • Moynagh, P. N., Bailey, C. J., Boyce, S. J., and Williams, D. C. (1991).Biochem. J. 275, 419–425.

    Google Scholar 

  • Nakashima, R. A., Mangan, P. S., Colombini, M., and Pedersen, P. L. (1986).Biochemistry 25, 1015–1021.

    Google Scholar 

  • Neckelmann, N., Li, K., Wade, R. P., Shuster, R., and Wallace, D. C. (1987).Proc. Natl. Acad. Sci. USA 84, 7580–7584.

    Google Scholar 

  • Novgorodov, S. A., Gudz, T. I., Kushnareva, Y. E., Zorov, D. B., and Kudrjashov, Y. B. (1990).FEBS Lett. 277, 123–126.

    Google Scholar 

  • Ohlendieck, K., Riesinger, I., Adams, V., Krause, J., and Brdiczka, D. (1986).Biochim. Biophys. Acta 860, 672–689.

    Google Scholar 

  • Olson, J. M. M., Ciliax, B. J., Mancini, W. R., and Young, A. B. (1988).Eur. J. Pharmacol. 152, 47–53.

    Google Scholar 

  • Papadopoulos, V., Mukhin, A. G., Costa, E., and Krueger, K. E. (1990).J. Biol. Chem. 265, 3772–3779.

    Google Scholar 

  • Papadopoulos, V., Nowzari, F. B., and Krueger, K. E. (1991).J. Biol. Chem. 266, 3682–3687.

    Google Scholar 

  • Parola, A. L., and Laird, H. E. (1991).Life Sci. 48, 757–764.

    Google Scholar 

  • Parola, A. L., Stump, D. G., Pepper, D. J., Krueger, K. E., Regan, J. W., and Laird, H. E. (1991).J. Biol. Chem. 266, 14082–14087.

    Google Scholar 

  • Parry, D. M., and Pedersen, P. L. (1983).J. Biol. Chem. 258, 10904–10912.

    Google Scholar 

  • Peterson, G. L., Rosenbaum, L. C., and Schimerlik, M. I. (1988).Biochem, J. 255, 553–560.

    Google Scholar 

  • Rassmussen, U. B., and Wohlrab, H. (1986).Biochim. Biophys. Acta 852, 306–314.

    Google Scholar 

  • Regan, J. W., Yamamura, H. I., Yamada, S., and Roeske, W. R. (1981).Life Sci. 28, 221–228.

    Google Scholar 

  • Riond, J., Vita, N., Le Fur, G., and Ferrara, P. (1989).FEBS Lett. 245, 238–244.

    Google Scholar 

  • Ruff, M. R., Pert, C. B., Weber, R. J., Wahl, L. M., and Paul, S. M. (1985).Science 229, 1281–1283.

    Google Scholar 

  • Safa, A. R., Glover, C. J., Sewell, J. L., Meyers, M. B., Bielder, J. L., and Felsted, R. L. (1987).J. Biol. Chem. 262, 7884–7888.

    Google Scholar 

  • Sandri, G., Siagri, M., and Panfili, E. (1988).Cell Calcium 9, 159–165.

    Google Scholar 

  • Skowronski, R., Beaumont, K., and Fanestil, D. D. (1987)Eur. J. Pharmacol. 143, 305–314.

    Google Scholar 

  • Snyder, S. H. (1986).Trends Neurosci. 9, 455–459.

    Google Scholar 

  • Snyder, S. H., and Verma, A. (1989).Annu. Rev. Pharmacol. Toxicol. 29, 307–322.

    Google Scholar 

  • Snyder, S. H., Verma, A., and Trifiletti, R. R. (1987).FASEB J. 1, 282–288.

    Google Scholar 

  • Snyder, S. H., McEnery, M. W., and Verma, A. (1990).Neurochem. Res. 15, 119–123.

    Google Scholar 

  • Sprengel, R., Werner, P., Seeburg, P. H., Mukhin, A. G., Santi, M. R., Grayson, D. R., Guidotti, A. A., and Krueger, K. E. (1989).J. Biol. Chem. 264, 20415–20421.

    Google Scholar 

  • Squires, R., and Braestrup, C. (1977).Nature (London)26, 732–734.

    Google Scholar 

  • Sterling, K. (1979).New Engl. J. Med. 300, 117–119.

    Google Scholar 

  • Sterling, K., Lazarus, J. H., Milch, P. O., Sakurada, T., and Brenner, M. A. (1978).Science 201, 1126–1129.

    Google Scholar 

  • Szabo, I., and Zoratti, M. (1991).J. Biol. Chem. 266, 3376–3379.

    Google Scholar 

  • Tallman, J. P., Paul, S. M., Skolnick, P., and Gallager, D. W. (1980).Science 207, 274–281.

    Google Scholar 

  • Verma, A., and Snyder, S. H. (1988).Mol. Pharmacol. 34, 800–805.

    Google Scholar 

  • Verma, A., Nye, J. S., and Snyder, S. H. (1987).Proc. Natl. Acac. Sci. USA 84, 2256–2260.

    Google Scholar 

  • Weiler, U., Riesinger, I., Knoll, G., and Brdiczka, D. (1985).Biochem. Med. 33, 223–235.

    Google Scholar 

  • Zernig, G. (1990).Trends Pharmacol. Sci. 11, 38–44.

    Google Scholar 

  • Zernig, G., Graziadei, I., Moshammer, T., Zech, C., Reider, N., and Glossmann, H. (1990).Mol. Pharmacol. 38, 362–369.

    Google Scholar 

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  1. Department of Neuroscience, The Johns Hopkins University School of Medicine, 21205, Baltimore, Maryland

    Maureen W. McEnery

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Abbreviations and chemical names: Ro5-4864: 7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4-benzodiazepin-2-one; Ro15-1788: ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-α]-[1,4]benzodiazepine-3-carboxylate; AHN-086: (1-(2-isothiocyanatoethyl-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepin-2-one hydrochloride;) PK11195: 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-isoquinoline-3-carboxamide; PK14105: 1-(2-fluoro-5-nitrophenyl)-3-isoquinoline-carboxylic acid.

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McEnery, M.W. The mitochondrial benzodiazepine receptor: Evidence for association with the voltage-dependent anion channel (VDAC). J Bioenerg Biomembr 24, 63–69 (1992). https://doi.org/10.1007/BF00769532

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