Adenine nucleotide translocation in liver mitochondria of hypothyroid rats

Abstract

In measurements using a disc filtration method, liver mitochondria obtained from hypothyroid rats translocate external ADP at 0 [deg]C via the atractyloside-sensitive carrier much more slowly than do mitochondria from normal rats, confirming the findings of Portnay et al. (Biochem. Biophys. Res. Commun. 55, 17, 1973). The hypothyroid mitochondria contain 60% more ATP + ADP than do mitochondria from normals, but the excess nucleotides are not exchangeable and so do not contribute to translocation. A decrease in the first-order rate constant accounts for the decreased velocity. Neither a decrease in the number of translocator sites nor changes in ADP phosphorylation or ATPase activity seem to account for the abnormal kinetics of translocation. Although the filtration method limits the maximal translocation rate observed in normal mitochondria at temperatures above 17 [deg]C that induce a fluid membrane state, no such transition is seen in mitochondria from hypothyroid rats up to 35 [deg]C, indicating that the translocator is in an altered environment in hypothyroidism. Injecting a hypothyroid rat once with -thyroxine corrects the abnormal compartmentation and produces a temperature-rate relationship like that in normal mitochondria in 3 days, a period which would accommodate the hormone actions reported on translation, membrane phospholipid synthesis, or fatty acid desaturation.