Mobilization of Mg2+ from rat heart and liver mitochondria following the interaction of thyroid hormone with the adenine nucleotide translocase.
The in vitro addition of thyroid hormone to isolated rat heart or liver mitochondria induces the extrusion of approximately 2-4 nmol Mg2+/mg protein from both mitochondria preparations. The mobilization of Mg2+ is not accompanied by extrusion of matrix ATP or K+, or by mitochondria swelling, thus excluding that the phenomenon occurs through the nonspecific opening of the mitochondrial permeability transition pore. Moreover, the Mg2+ extrusion is completely prevented by bongkrekic acid, a membrane-permeant inhibitor of the adenine nucleotide translocase (AdNT), and by cyclosporine, which has also been reported to inhibit AdNT in a bongkrekate-like manner, operating at the matrix site of the translocase. By contrast, atractyloside, another specific inhibitor of AdNT that operates at the cytosolic site of the AdNT, only partially affects the Mg2+ mobilization (< 30% inhibition). These findings and the binding of 125I-labeled thyroid hormone to both the dimeric and monomeric moiety of AdNT support the hypothesis that AdNT can operate as a specific receptor for thyroid hormone in the mitochondria, and suggest that thyroid hormone operates at the matrix site of the translocase. In addition, these observations may imply that some of the so called "nongenomic effects" exerted by thyroid hormone on mitochondrial metabolism could occur through changes in the matrix content of Mg2+.
Romani
A
A
Department of Physiology and Biophysis, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Marfella
C
C
Lakshmanan
M
M
D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D001865:Bongkrekic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D001865:Bongkrekic Acid; D001278:Atractyloside; D000226:Mitochondrial ADP, ATP Translocases; D008274:Magnesium