Effects of Taurine and Structurally Related Analogues on Ca2+ Uptake and Respiration Rate in Rat Liver Mitochondria
Mitochondria from vertebrate sources possess an elaborate system for transporting Ca2+ across their inner membrane. This process includes accumulation of the cation into their matrix, via an uniporter mechanism. This is balanced by electroneutral Ca2+ release mediated by the functioning of a 2 Na+:1 Ca2+ exchanger or “antiporter” in mitochondria from most tissues, including heart, brain and brown adipose tissue, or by a 2H+/Ca2+ antiporter in liver7. In addition to these functions, mitochondria produce about 95% of the common cellular energy as ATP by means of oxidative phosphorylation. Under physiological conditions, Ca2+ transport and energy production seem to be strictly correlated and there is convincing evidence that the intramitochondrial Ca2+ concentration functions as a metabolic control in signalling the mitochondria to modify its metabolic rate in response to increased energy demand. According to the theory of flux control, the steps of Ca2+-mediated metabolic control are distributed and include activation of the Ca2+-sensitive dehydrogenases2, 9 and other Ca2+-sensitive metabolic processes8, 16. In this context, drugs that alter the flux of Ca2+ across mitochondrial membranes could, in theory, play a role in modulating the cellular energetic metabolism.
KeywordsBrown Adipose Tissue Mitochondrial Oxidative Phosphorylation Proton Leak Couple Respiration Isethionic Acid
Unable to display preview. Download preview PDF.
- 2.Denton, R.M. and McCormack, J.G. 1985, Ca2+ transport by mammalian mitochondria and its role in hormone action. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E 543–E 554.Google Scholar
- 3.Chappell J.B. and Hansford, R.G. 1972, Preparation of mitochondria from animal tissues and yeast, in: “Subcellular Components: Preparation and Fractionation”, 2nd Ed., Birmie G.D. ed., London: Butter-worth, pp. 77–91 (1972).Google Scholar
- 4.Fusi, F. Valoti, M., Sgaragli G.P. and Murphy, M.P. 1991, The interactions of antioxidants and structurally related compounds with mitochondrial oxidative phosphorylation. Meth. Exp. Pharmacol. 13: 599–603.Google Scholar
- 5.Gornall, A.G., Bardawill C.J. and David, M.M. 1949, Determination of serum protein by means of the biuret reaction. J. Biol. Chem. 177: 751–766.Google Scholar
- 6.Gunter, T.E., Gunter, K.K., Shey-Shing, S. and Gavin, C.E. 1994, Mitochondrial calcium transport: physiological and pathological relevance. Am. J. Physiol. 267 (Cell Physiol. 36): C313–C339.Google Scholar
- 7.Gunter T.E. and Pfeiffer, D.R. 1990, Mechanism by which mitochondria transport calcium. Am J. Physiol., 258 (Cell Physiol. 27): C755–C786.Google Scholar
- 11.Huxtable, R. J. 1987, From heart to hypothesis: a mechanism for the calcium modulatory actions of taurine, in: “The Biology of Taurine: Methods and Mechanisms”, R.J. Huxtable, F. Franconi and A. Giotti eds., New York: Plenum Press, pp. 371–388.Google Scholar
- 14.Kuriyama, K., Muratmatsu, M., Nakagawa K. and Kakita, K. 1978, Modulating role of taurine on release of neurotransmitters and calcium transport in excitable tissues, in: “Taurine and Neurological Disorders”, A. Barbeau and R.J Huxtable, eds, New York: Raven Press, pp. 201–216.Google Scholar
- 16.McCormack, J.G., Halestrap A.P. and Denton, R.M. 1990, Role of calcium ions in the regulation of mammalian intramitochondrial metabolism. Physiol. Rev. 70: 391–425.Google Scholar
- 18.Palade, P. 1986, Drug-induced Ca2+ release from isolated sarcoplasmic reticulum by use of pyrophosphate to study caffeine-induced Ca2+ release. J. Biol. Chem., 282: 6135–6141.Google Scholar
- 22.Sebring, L. and Huxtable, R.J. 1985, Taurine modulation of calcium binding to cardiac sarcolemma. J. Pharmacol. Exp. Ther. 232: 445–451.Google Scholar