MOBILIZATION OF MG2-HEART AND LIVER-MITOCHONDRIA FOLLOWING THE INTERACTION OF THYROID-HORMONE WITH THE ADENINE-NUCLEOTIDE TRANSLOCASE( FROMRAT)

The in vitro addition of thyroid hormone to isolated rat heart or live r mitochondria induces the extrusion of similar to 2-4 nmol Mg2+/mg pr otein 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 nonspe cific opening of the mitochondrial permeability transition pore. Moreo ver, the Mg2+ extrusion is completely prevented by bongkrekic acid, a membrane-permeant inhibitor of the adenine nucleotide translocase (AdN T), and by cyclosporine, which has also been reported to inhibit AdNT in a bongkrekate-like manner, operating at the matrix site of the tran slocase. By contrast, atractyloside, another specific inhibitor of AdN T that operates at the cytosolic site of the AdNT, only partially affe cts the Mg2+ mobilization (<30% inhibition). These findings and the bi nding of I-125-labeled thyroid hormone to both the dimeric and monomer ic moiety of AdNT support the hypothesis that AdNT can operate as a sp ecific receptor for thyroid hormone in the mitochondria, and suggest t hat thyroid hormone operates at the matrix site of the translocase. In addition, these observations may imply that some of the so called ''n ongenomic effects'' exerted by thyroid hormone on mitochondrial metabo lism could occur through changes in the matrix content of Mg2+.