In Vitro and In Vivo Activation of Mitochondrial Membrane Permeability Transition Pore Using Triiodothyronine

Abstract

Using a novel method for evaluating mitochondrial swelling (Drahota et al. 2012a) we studied the effect of calcium (Ca2+), phosphate (Pi), and triiodothyronine (T3) on the opening of mitochondrial membrane permeability transition pore and how they interact in the activation of swelling process. We found that 0.1 mM Pi, 50 µM Ca2+ and 25 µM T3 when added separately increase the swelling rate to about 10 % of maximal values when all three factors are applied simultaneously. Our findings document that under experimental conditions in which Ca2+ and Pi are used as activating factors, the addition of T3 doubled the rate of swelling. T3 has also an activating effect on mitochondrial membrane potential. The T3 activating effect was also found after in vivo application of T3. Our data thus demonstrate that T3 has an important role in opening the mitochondrial membrane permeability pore and activates the function of the two key physiological swelling inducers, calcium and phosphate ions.