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

Abstract

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.

Authors:
 [1];  [2];  [2];  [2];  [2];  [2];  [3];  [3];  [2];  [2]
  1. Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States). E-mail: shamina.rangwala@novartis.com
  2. Diabetes and Metabolism Disease Area, Novartis Institutes of BioMedical Research Institutes, 100 Technology Square, Cambridge, MA 02139 (United States)
  3. Genome and Proteome Sciences, Novartis Institutes of BioMedical Research Institutes, 500 Technology Square, Cambridge, MA 02139 (United States)
Publication Date:
OSTI Identifier:
20991357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 357; Journal 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)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; CARNITINE; CITRATES; ENZYME ACTIVITY; ESTROGENS; FIBROBLASTS; GENES; METABOLISM; MICE; MITOCHONDRIA; OXIDASES; OXIDATION; PHOSPHORYLATION; RECEPTORS; SUPEROXIDE DISMUTASE

Citation Formats

Rangwala, Shamina M., Li, Xiaoyan, Lindsley, Loren, Wang, Xiaomei, Shaughnessy, Stacey, Daniels, Thomas G., Szustakowski, Joseph, Nirmala, N.R., Wu, Zhidan, and Stevenson, Susan C. Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.03.126.
Rangwala, Shamina M., Li, Xiaoyan, Lindsley, Loren, Wang, Xiaomei, Shaughnessy, Stacey, Daniels, Thomas G., Szustakowski, Joseph, Nirmala, N.R., Wu, Zhidan, & Stevenson, Susan C. Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function. United States. doi:10.1016/j.bbrc.2007.03.126.
Rangwala, Shamina M., Li, Xiaoyan, Lindsley, Loren, Wang, Xiaomei, Shaughnessy, Stacey, Daniels, Thomas G., Szustakowski, Joseph, Nirmala, N.R., Wu, Zhidan, and Stevenson, Susan C. Fri . "Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function". United States. doi:10.1016/j.bbrc.2007.03.126.
@article{osti_20991357,
title = {Estrogen-related receptor {alpha} is essential for the expression of antioxidant protection genes and mitochondrial function},
author = {Rangwala, Shamina M. and Li, Xiaoyan and Lindsley, Loren and Wang, Xiaomei and Shaughnessy, Stacey and Daniels, Thomas G. and Szustakowski, Joseph and Nirmala, N.R. and Wu, Zhidan and Stevenson, Susan C.},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2007.03.126},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 357,
place = {United States},
year = {Fri May 25 00:00:00 EDT 2007},
month = {Fri May 25 00:00:00 EDT 2007}
}