Potentiation of mitochondrial Ca2+ sequestration by taurine

The effects of taurine (2-aminoethanesulphonic acid) and its analogues, 2-a minoethylarsonic acid, 2-hydroxyethanesulphonic (isethionic) acid, 3-aminop ropanesulphonic acid, 2-aminoethylphosphonic acid, and N,N-dimethyltaurine, were studied on the transport of Ca2+ by mitochondria isolated from rat li ver. Taurine enhanced Ca2+ uptake in an apparently saturable process, with a K-m value of about 2.63 mM. Taurine behaved as an uncompetitive activator of Ca2+ uptake, increasing both the apparent K-m and V-max values of the p rocess. This effect was not modified in the presence of cyclosporin A (CsA) . N,N-Dimethyltaurine also stimulated Ca2+ uptake at higher concentrations, but there was no evidence that the process was saturable over the concentr ation range used (1-10 mM). Aminoethylarsonate was a weak inhibitor of basa l Ca2+ uptake, but inhibited that stimulated by taurine in an apparently co mpetitive fashion (K-f = 0.05 mM). The other analogues had no significant e ffects on this process. Taurine either in the presence or the absence of Cs A had no effect on Ca2+ release induced by 200 nM ruthenium red. Thus, the mechanism of taurine-enhanced Ca2+ accumulation appears to involve stimulat ion of Ca2+ uptake via the uniport system rather than inhibition of Ca2+ re lease via the ion (Na+/Ca2+ and/or H+/Ca2+) exchangers or by taurine modula ting the permeability transition of the mitochondrial inner membrane. Overa ll, these findings indicate an interaction of taurine with an as yet uniden tified mitochondrial site which might regulate the activity of the uniporte r. The unique role of taurine in modulating mitochondrial Ca2+ homeostasis might be of particular importance under pathological conditions that are ch aracterised by cell Ca2+ overload, such as ischaemia and oxidative stress. (C) 1999 Elsevier Science Inc.