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Publication : Estrogen-related receptor alpha is essential for the expression of antioxidant protection genes and mitochondrial function.

First Author  Rangwala SM Year  2007
Journal  Biochem Biophys Res Commun Volume  357
Issue  1 Pages  231-6
PubMed ID  17418099 Mgi Jnum  J:121787
Mgi Id  MGI:3711617 Doi  10.1016/j.bbrc.2007.03.126
Citation  Rangwala SM, et al. (2007) Estrogen-related receptor alpha is essential for the expression of antioxidant protection genes and mitochondrial function. Biochem Biophys Res Commun 357(1):231-6
abstractText  Estrogen-related receptor alpha (ERRalpha) is an important mediator of mitochondrial biogenesis and function. To investigate the transcriptional network controlling these phenomena, we investigated mitochondrial gene expression in embryonic fibroblasts isolated from ERRalpha null mice. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) stimulated mitochondrial gene expression program in control cells, but not in the ERRalpha null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1alpha levels was dependent on ERRalpha. Furthermore, we found that the PGC-1alpha-mediated induction of estrogen-related receptor gamma and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERRalpha. Basal levels of NRF-2 were decreased in the absence of ERRalpha. The absence of ERRalpha resulted in a decrease in citrate synthase enzyme activity in response to PGC-1alpha overexpression. Our results indicate an essential role for ERRalpha as a key regulator of oxidative metabolism.
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