Abstract
Low levels of ADP binding at the ADP/ATP translocase caused inhibition of the Ca2+-inducedpermeability transition of the mitochondrial inner membrane, when measured using the shrinkage assay on mitochondria, which have already undergone a transition. Inhibition was preventedby carboxyatractyloside, but potentiated by bongkrekic acid, which increased the affinity forinhibition by ADP. This suggests that inhibition was related to the conformation of thetranslocase. Ca2+ addition was calculated to remove most of the free ADP. Ca2+ added after ADPinduced a slow decay of the inhibition, which probably reflected the dissociation of ADP fromthe translocator. We conclude that the probability of forming a permeability transition pore(PTP) is much greater when the translocase is in the CAT conformation than in the BKAconformation, and, in the absence of CAT and BKA, the translocator is shifted between theBKA and CAT conformations by ADP binding and removal, even in deenergized mitochondria with no nucleotide gradients.
Similar content being viewed by others
REFERENCES
Bers, D. M., Patton, C. W., and Nuccitelli, R. (1994). Methods Cell Biol. 40, 3-29.
Beutner, G., Rück, A., Riede, B., Welte, W., and Brdiczka, D. (1996). FEBS Lett. 396, 189-195.
Brustovetsky, N., and Klingenberg, M. (1996). Biochemistry 35, 8483-8488.
Buchanan, B. B., Eiermann, W., Riccio, P., Aquila, H., and Klingenberg, M. (1976). Proc. Natl. Acad. Sci. USA 73, 2280-2284.
Crompton, M., Virji, S., and Ward, J. M. (1998). Eur. J. Biochem. 258, 729-735
Fiore, C., Trezeguet, V., Le Saux, A., Roux, P., Schwimmer, C., Dianoux, A. C., Noel, F., Lauquin, G. J. M., Brandolin, G., and Vignais, P. V. (1998). Biochimie 80, 137-150.
Halestrap, A. P., Woodfield, K.-Y., and Connern, C. P. (1997). J. Biol. Chem. 272, 3346-3354.
Haworth, R. A., and Hunter, D. R. (1979). Arch. Biochem. Biophys. 195, 460-467.
Haworth, R. A., and Hunter, D. R. (1980a). J. Membr. Biol. 54, 231-236.
Haworth, R. A., and Hunter, D. R. (1980b). Fed. Proc. 39, 1707.
Hunter, D. R., Haworth, R. A., and Southard, J. H. (1976). J. Biol. Chem. 251, 5069-5077.
Hunter, D. R., and Haworth, R. A. (1979). Arch. Biochem. Biophys. 195, 453-459.
Le Quoc, K., and Le Quoc, D. (1988). Arch. Biochem. Biophys. 265, 249-257.
Le Quoc, D., and Le Quoc, K. (1989). Arch. Biochem. Biophys. 273, 466-478.
Leblanc, P., and Clauser, H. (1972). FEBS Lett. 23, 107-113.
Novgorodov, S. A., Gudz, T. I., Brierley, G. P., and Pfeiffer, D. R. (1994). Arch. Biochem. Biophys. 311, 219-228.
Novgorodov, S. A., Gudz, T. I., Milgrom, Y. M., and Brierley, G. P. (1992). J. Biol. Chem. 267, 16274-16282.
Petronilli, V., Cola, C., Massari, S., Colonna, R., and Bernardi, P. (1993). J. Biol. Chem. 268, 21939-21945.
Ruck, A., Dolder, M., Wallimann, T., and Brdiczka, D. (1998). FEBS Lett. 426, 97-101.
Weidemann, M. J., Erdelt, H., and Klingenberg, M. (1970). Biochem. Biophys. Res. Commun. 39, 363-370.
Woodfield, K., Ruck, A., Brdiczka, D., and Halestrap, A. P. (1998). Biochem. J. 336, 287-290.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Haworth, R.A., Hunter, D.R. Control of the Mitochondrial Permeability Transition Pore by High-Affinity ADP Binding at the ADP/ATP Translocase in Permeabilized Mitochondria. J Bioenerg Biomembr 32, 91–96 (2000). https://doi.org/10.1023/A:1005568630151
Issue Date:
DOI: https://doi.org/10.1023/A:1005568630151