Abstract
The recent finding that the inhibition of Ca2+-stimulated respiration by ruthenium red is mainlydue to a binuclear ruthenium complex (Ru360) present in the commercial samples of the classicalinhibitor ruthenium red (Ying et. al., 1991), showed that this complex is the more potent andspecific inhibitor of the mitochondrial calcium uniporter. This work was aimed to provideinsights into the mechanism by which Ru360 and other ruthenium-related compounds inhibitscalcium uptake. Ruthenium red and a synthesized analog (Rrphen) were compared with Ru360.The inhibition by this binuclear complex was noncompetitive, with a K i of 9.89 nM. Thenumber of specific binding sites for Ru360 was 6.2 pmol/mg protein. Ruthenium red and Ru360were mutually exclusive inhibitors. Bound La3+ was not displaced by Ru360. Rrphen was theleast effective for inhibiting calcium uptake. The results support the notion of a specific bindingsite in the uniporter for the polycationic complexes and a negative charged region from thephospholipids in the membrane, closely associated with the uniporter inhibitor-binding site.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Carrondo, M., Griffith, W., Hall, J., and Skalski, A. (1980). Biochim. Biophys. Acta 627, 332-334.
Chávez, E., Briones, R., Michel, B., Bravo, C., and Jay, D. (1985). Arch. Biochem. Biophys. 242, 493-497.
Gibson, J., Poole, R., Hughes, M., and Rees, J. (1982). J. Gen. Microbiol. 128, 2211-2214.
Halestrap, A. P. (1987). Biochem. J. 244, 159-164.
Hansford, R. (1994). J. Bioenerg. Biomembr. 26, 495-508.
Litsky, M., and Pfeiffer, D. (1997). Biochemistry 38, 7071-7080.
Luft, J. H. (1971). Anat. Rec. 171, 347-368.
Matlib, M., Zhou, Z., Knight, S., Ahmed, S., Choi, K., Krause-Bauer, J., Phillips, R., Altschuld, R., Katsube, Y., Sperelakis, N., and Bers, D. (1998). J. Biol. Chem. 273, 10223-10231.
McCormack, J., Halestrap, A., and Denton, R. (1990). Physiol. Rev. 70, 391-425.
Missiaen, L., DeSmedt, H., Droogmans, F., Wuytack, F., Raeymarckers, L., and Casteels, R. (1990). Biochim. Biophys. Acta 1023, 449-454.
Moreno-Sánchez, R. (1985). J. Biol. Chem. 260, 4028-4034.
Panov, A., and Scaduto, R. C., Jr. (1995). Arch. Biochem. Biophys. 316, 815-820.
Reed, K., and Bygrave, F. (1974). Biochem. J. 140, 143-155.
Rizzuto, R., Brini, M., Murgía, M., and Pozzan, T. (1993). Science 262, 744-747.
Segel, I. Enzyme Kinetics, Wiley (Interscience), New York, 1993, p. 947.
Sparagna, G., Gunter, K., Shen, S., and Gunter, T. (1995). J. Biol. Chem. 270, 27510-27515.
Tashmukhamedov, G., Gagelgans, A., Mamatkulov, Kh., and Makhmudova, E. (1972). FEBS Lett. 28, 239-242.
Tatulian, S. (1994). J. Phys. Chem. 98, 4963-4965.
Voelker, D., and Smejtek, P. (1996). Biophys. J. 70, 818-830.
White, R., and Reynolds, I. (1995). J. Neurosci 15, 1318-1328.
Yamada, E., and Huzel, N. (1988). J. Biol. Chem. 263, 11498-11503.
Ying, W., Emerson, J., Clarke, M., and Sanadi, R. (1991). Biochemistry 30, 4949-4952.
Zazueta, C., Zafra, G., Vera, G., Sánchez, C., and Chávez, E. (1998). J. Bioenerg. Biomembr. 30, 489-498.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zazueta, C., Sosa-Torres, M.E., Correa, F. et al. Inhibitory Properties of Ruthenium Amine Complexes on Mitochondrial Calcium Uptake. J Bioenerg Biomembr 31, 551–557 (1999). https://doi.org/10.1023/A:1005464927366
Issue Date:
DOI: https://doi.org/10.1023/A:1005464927366