Mitochondrial permeability transition is induced by in vivo thyroid hormone treatment

Thyroid hormone treatment in vivo results in activation of mitochondrial Ca2+ efflux and temperature-dependent enhanced swelling of Ca(2+)-loaded rat liver mitochondria. Thyroid hormone-induced swelling was effectively prevented in the presence of excess EGTA or cyclosporin A. Thyroid hormone treatment similarly resulted in a dramatic decrease in mitochondrial membrane potential (80%), proton gradient (45%), and proton motive force (69%) measured in Ca(2+)-loaded mitochondria. All three parameters were essentially restored to euthyroid values in the presence of excess EGTA or cyclosporin A. Mitochondrial energy-linked transhydrogenase activity measured in the presence of Ca2+ was 33% increased and 38% decreased in hypothyroid and L-T3-treated hypothyroid rats, respectively, compared to that in euthyroid rats. Hence, in vivo thyroid hormone treatment may induce mitochondrial permeability transition mediated by the cyclosporin A-sensitive permeability transition pore.