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.
Kalderon
B
B
Department of Human Nutrition and Metabolism, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Hermesh
O
O
Bar-Tana
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004734:Energy Metabolism; D007037:Hypothyroidism / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D009250:NADP Transhydrogenases / Q000378:metabolism; D010539:Permeability; D051381:Rats; D012016:Reference Values; D013696:Temperature; D013963:Thyroid Hormones / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
D013963:Thyroid Hormones; D014284:Triiodothyronine; D004533:Egtazic Acid; D016572:Cyclosporine; D009250:NADP Transhydrogenases; D002118:Calcium