Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function

Journal Article · Fri May 25 00:00:00 EDT 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.03.126· OSTI ID:20991357

Rangwala, Shamina M ^[1]; Li, Xiaoyan ^[1]; Lindsley, Loren ^[1]; Wang, Xiaomei ^[1]; Shaughnessy, Stacey ^[1]; Daniels, Thomas G ^[1]; Szustakowski, Joseph ^[2]; Nirmala, N R ^[2]; Wu, Zhidan ^[1]; Stevenson, Susan C ^[1]

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1. Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States)
2. Genome and Proteome Sciences, Novartis Institutes of BioMedical Research Institutes, 500 Technology Square, Cambridge, MA 02139 (United States)

Estrogen-related receptor {alpha} (ERR{alpha}) 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 ERR{alpha} null mice. Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) stimulated mitochondrial gene expression program in control cells, but not in the ERR{alpha} null cells. Interestingly, the induction of levels of mitochondrial oxidative stress protection genes in response to increased PGC-1{alpha} levels was dependent on ERR{alpha}. Furthermore, we found that the PGC-1{alpha}-mediated induction of estrogen-related receptor {gamma} and nuclear respiratory factor 2 (NRF-2), was dependent on the presence of ERR{alpha}. Basal levels of NRF-2 were decreased in the absence of ERR{alpha}. The absence of ERR{alpha} resulted in a decrease in citrate synthase enzyme activity in response to PGC-1{alpha} overexpression. Our results indicate an essential role for ERR{alpha} as a key regulator of oxidative metabolism.

• OSTI ID: 20991357
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 357, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.03.126; PII: S0006-291X(07)00612-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIOXIDANTS
CARNITINE
CITRATES
ENZYME ACTIVITY
ESTROGENS
FIBROBLASTS
GENES
METABOLISM
MICE
MITOCHONDRIA
OXIDASES
OXIDATION
PHOSPHORYLATION
RECEPTORS
SUPEROXIDE DISMUTASE