Thyroid hormone increases transcription of GA-binding protein/nuclear respiratory factor-2 alpha-subunit in rat liver

Thyroid hormone (TH) regulates mitochondrial respiratory rate by activating coordinated transcription in the nucleus and mitochondria. Whereas TH activates transcription of mitochondrial genes directly, the activation of nuclear-encoded mitochondrial genes is probably executed by indirect unknown mechanisms. Nuclear respiratory factors (NRF)-1 and GA-binding protein (BP)/NRF-2 may function as transacting genes, but regulation of these genes by TH is not demonstrated. We show that TH administration to hypothyroid rats promptly increases GABP/NRF-2 alpha-subunit mRNA levels in the liver, without significant changes in beta, gamma subunits. In run-on and time-course experiments, the transcription rate and protein levels increased three-fold in response to TH, indicating GABP/NRF-2 transcriptional regulation. The results also support the notion that ATP synthase beta-subunit is regulated by TH through the indirect activation of GABP/NRF-2.