Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals

Abstract

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Mitochondrial Biogenesis through Activation of Nuclear Signaling Proteins

“…This includes mitochondrial-driven thermogenesis that occurs in brown fat during the adaptation to lower temperatures (Silva 1995). In some instances, THRs directly drive the transcription of nuclear-encoded genes, whereas, in others, the effects can occur indirectly through the thyroid hormone-mediated up-regulation of NRF-1 (Venditti et al 2009). A truncated form of thyroid hormone receptor a has been reported to be localized to the mitochondrion and may serve to directly activate the transcription of genes in the mitochondrial genome (Casas et al 1999).…”

Oxidative stress in cold-induced hyperthyroid state

“…The results of this study did not support the idea that thyroxine was a factor responsible for cold-linked mitochondrial proliferation. Indeed, T 4 treatment did not increase mitochondrial proteins that, conversely, were increased by cold exposure of T 3 -treated rats in which T 4 plasma levels were low (Venditti et al, 2009).…”

Coordination of mitochondrial biogenesis by thyroid hormone

“…Knock-out of NRF-1 is embryonic lethal associated with dramatically reduced number and function of mitochondria (Huo and Scarpulla, 2001). NRF-1 is rapidly and robustly regulated by TH (Venditti et al, 2009;Weitzel et al, 2001) and thus NRF-1 is clearly one of the factors which translate TH effects. Very similar observations have been made with NRF-2 (also known as GA-binding protein, GABP).…”

“…Whereas the beta subunit is only slightly regulated within 6 hours (Weitzel et al, 2001), the alpha subunit has been described to be positively and negatively regulated after 3 and 10 days, respectively (Rodriguez-Pena et al, 2002;Venditti et al, 2009). Knock-out of NRF-2α in mice leads to early embryonic lethality showing a very similar phenotype as NRF-1 knockouts (Ristevski et al, 2004).…”

“…PGC-1α is rapidly and robustly induced by TH both on transcript (13-fold) and protein levels (3-fold) (Irrcher et al, 2003;Weitzel et al, 2003;Venditti et al, 2009), this regulation is mediated by a TRE in the gene promoter (Wulf et al, 2008). Interestingly, PGC-1α has also been described to be located into the mitochondria; however, more experimental evidence is needed to clarify this issue (Aquilano et al, 2010).…”