Thyroxine induces cyclosporin A-insensitive, Ca2+-dependent reversible permeability transition pore in rat liver mitochondria.
The effect of thyroxine on Ca2+-dependent mitochondrial permeability transition has been examined. It is shown that 40 microM thyroxine induces high amplitude swelling and decrease in membrane potential in Ca2+-loaded rat liver mitochondria, both in the presence and absence of cyclosporin A. Thyroxine-induced decrease in membrane potential is partially or completely reversed by addition of EGTA into the incubation medium. Nigericin and ADP are shown to prevent, or significantly delay, the effects of thyroxine on both mitochondrial swelling and membrane potential, whereas nicotinamide potentiates the permeabilisation of mitochondria. It is suggested that thyroxine induced reversible, cyclosporin A-insensitive permeability transition pore (PTP) opening in the inner mitochondrial membrane.
Malkevitch
N V
NV
Department of Bioenergetics, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia.
Dedukhova
V I
VI
Simonian
R A
RA
Skulachev
V P
VP
Starkov
A A
AA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000648:ultrastructure*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009536:Niacinamide / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013974:Thyroxine / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology
D007476:Ionophores; D014475:Uncoupling Agents; D009536:Niacinamide; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D013974:Thyroxine; D009550:Nigericin; D002118:Calcium