Potentiation of mitochondrial Ca 2+ sequestration by taurine

Abstract

The effects of taurine (2-aminoethanesulphonic acid) and its analogues, 2-aminoethylarsonic acid, 2-hydroxyethanesulphonic (isethionic) acid, 3-aminopropanesulphonic acid, 2-aminoethylphosphonic acid, and N, N-dimethyltaurine, were studied on the transport of Ca 2+ by mitochondria isolated from rat liver. Taurine enhanced Ca 2+ uptake in an apparently saturable process, with a K m value of about 2.63 mM. Taurine behaved as an uncompetitive activator of Ca 2+ uptake, increasing both the apparent K m and V max values of the process. This effect was not modified in the presence of cyclosporin A (CsA). N, N-Dimethyltaurine also stimulated Ca 2+ uptake at higher concentrations, but there was no evidence that the process was saturable over the concentration range used (1–10 mM). Aminoethylarsonate was a weak inhibitor of basal Ca 2+ uptake, but inhibited that stimulated by taurine in an apparently competitive fashion ( K i = 0.05 mM). The other analogues had no significant effects on this process. Taurine either in the presence or the absence of CsA had no effect on Ca 2+ release induced by 200 nM ruthenium red. Thus, the mechanism of taurine-enhanced Ca 2+ accumulation appears to involve stimulation of Ca 2+ uptake via the uniport system rather than inhibition of Ca 2+ release via the ion (Na +/Ca 2+ and/or H +/Ca 2+) exchangers or by taurine modulating the permeability transition of the mitochondrial inner membrane. Overall, these findings indicate an interaction of taurine with an as yet unidentified mitochondrial site which might regulate the activity of the uniporter. The unique role of taurine in modulating mitochondrial Ca 2+ homeostasis might be of particular importance under pathological conditions that are characterised by cell Ca 2+ overload, such as ischaemia and oxidative stress.