TY - JOUR
T1 - The estrogen-related receptor α (ERRα) functions in PPARγ coactivator 1α (PGC-1α)-induced mitochondrial biogenesis
AU - Schreiber, Sylvia N.
AU - Emter, Roger
AU - Hock, M. Benjamin
AU - Knutti, Darko
AU - Cardenas, Jessica
AU - Podvinec, Michael
AU - Oakeley, Edward J.
AU - Kralli, Anastasia
PY - 2004/4/27
Y1 - 2004/4/27
N2 - Estrogen-related receptor α (ERRα) is one of the first orphan nuclear receptors to be identified, yet its physiological functions are still unclear. We show here that ERRα is an effector of the transcriptional coactivator PGC-1α [peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Inhibition of ERRα compromises the ability of PGC-1α to induce the expression of genes encoding mitochondrial proteins and to increase mitochondrial DNA content. A constitutively active form of ERRα is sufficient to elicit both responses. ERRα binding sites are present in the transcriptional control regions of ERRα/PGC-1α-induced genes and contribute to the transcriptional response to PGC-1α. The ERRα-regulated genes described here have been reported to be expressed at reduced levels in humans that are insulin-resistant. Thus, changes in ERRα activity could be linked to pathological changes in metabolic disease, such as diabetes.
AB - Estrogen-related receptor α (ERRα) is one of the first orphan nuclear receptors to be identified, yet its physiological functions are still unclear. We show here that ERRα is an effector of the transcriptional coactivator PGC-1α [peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Inhibition of ERRα compromises the ability of PGC-1α to induce the expression of genes encoding mitochondrial proteins and to increase mitochondrial DNA content. A constitutively active form of ERRα is sufficient to elicit both responses. ERRα binding sites are present in the transcriptional control regions of ERRα/PGC-1α-induced genes and contribute to the transcriptional response to PGC-1α. The ERRα-regulated genes described here have been reported to be expressed at reduced levels in humans that are insulin-resistant. Thus, changes in ERRα activity could be linked to pathological changes in metabolic disease, such as diabetes.
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U2 - 10.1073/pnas.0308686101
DO - 10.1073/pnas.0308686101
M3 - Article
C2 - 15087503
AN - SCOPUS:2342592545
SN - 0027-8424
VL - 101
SP - 6472
EP - 6477
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -