EVIDENCE FOR THE PRESENCE OF ALPHA-RELATED AND BETA-RELATED T(3)-RECEPTORS IN RAT-LIVER MITOCHONDRIA

Although the dependence of mitochondrial structure and function on thy roid hormone status is well established, several attempts to demonstra te a direct pathway of T3 action on mitochondria have been made during the last decade without being firmly conclusive. In this study, we pr esent evidence firstly for the presence of specific binding sites for [I-125]-T3 in rat liver mitochondria 5 min after injection, as assesse d by ultrastructural autoradiography. In the same way, using immunocyt ological techniques and protein immunoblotting, T3 receptor-like immun oreactivity was revealed mainly in the nucleus and mitochondria of hep atocytes. Whereas the colloidal gold labeling over mitochondria was fo und to be specific at the ultrastructural level, these results were co nfirmed biochemically by Western blotting experiments which revealed t he presence of two protein bands in mitochondria: a stronger one of 55 kDa and a weaker one of 48 kDa. At the opposite, receptor T3 mRNAs we re not detected in mitochondria by ultrastructural in situ hybridizati on thus confirming that the synthesis of receptor T3 occurs in the cyt oplasm and that nuclear-encoded T3 receptors may belong to the bulk of cytosolic precursor polypeptides which are targeted to and imported i nto mitochondria. These results confirm that a direct pathway of T3 ac tion on mitochondria occurs in situ which could now explain how the ra pid activation of several mitochondrial functions can take place withi n minutes after thyroid hormone injection.