Dependence of the mitochondrial uptake of triiodothyronine (T3) in rat kidney on cytosolic T3-binding protein.

The effect of cytosolic T3-binding protein (CTBP) on mitochondrial T3 uptake was investigated by using rat kidney tissue in vitro. [125I]T3 uptake into mitochondria was time dependent in the absence of CTBP. Addition of CTBP to the incubation medium significantly increased mitochondrial [125I]T3 uptake. When mitochondria were incubated with a [125I]T3-CTBP complex, [125I]T3 uptake into mitochondria continued to be time dependent, but the amount of [125I]T3 incorporated was greater than in mitochondria incubated with free [125I]T3. Although [125I]T3 uptake was not significantly inhibited by an excess of unlabeled T3, it was markedly inhibited by an excess of unlabeled T3-CTBP complex. The degree of inhibition was related to the concentration of T3-CTBP complex. However, [125I]T3 uptake produced by incubation of mitochondria with [125I]T3-CTBP complex was not inhibited by unsaturated CTBP. [125I]T3 binding to outer mitochondrial membranes was observed when the membranes were incubated with free [125I]T3 or [125I]T3-CTBP complex; the amount of [125I]T3 bound was greater in the membranes incubated with [125I]T3-CTBP complex. [125I]T3 binding to the membranes incubated with [125I]T3-CTBP complex was displaced by the addition of unlabeled T3-CTBP complex. These results suggest that mitochondrial T3 uptake is mediated by previous binding of T3 to CTBP, and that the uptake is possibly regulated by T3-CTBP complex binding to its receptor in the outer mitochondrial membrane.