Nobiletin restores impaired hippocampal mitochondrial bioenergetics in hypothyroidism through activation of matrix substrate-level phosphorylation.

Objective: Evaluation of the effect of citrus flavonoid - nobiletin on the bioenergetics of synaptic and non-synaptic mitochondria in the hippocampus of hypothyroid rats.

Methods: Male Wistar rats were divided into hypothyroid (methimazole-treated), nobiletin supplemented hypothyroid, thyroxine-treated hypothyroid, and euthyroid (control) groups. Synaptic and non-synaptic (cell) mitochondria were isolated from hippocampus.

Social isolation in rats inhibits oxidative metabolism, decreases the content of mitochondrial K-Ras and activates mitochondrial hexokinase.

Recent observations have suggested that Ras signaling includes combinations of extracellular-signal-regulated Ras activation at the plasma membrane and endomembranes, and translocation of Ras from the plasma membrane to intracellular compartments. In this study we have shown that social isolation of rat decreases the content of Bcl-2-associated K-Ras in hippocampal mitochondria, whereas the amount of H-Ras is increased in the microsomal fraction. Furthermore, we have found that galectin 1, a binding partner of activated Ras, was increased in the soluble fractions.