PT  - JOURNAL ARTICLE
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
TI  - The estrogen-related receptor α (ERRα) functions in PPARγ coactivator 1α (PGC-1α)-induced mitochondrial biogenesis
AID  - 10.1073/pnas.0308686101
DP  - 2004 Apr 27
TA  - Proceedings of the National Academy of Sciences of the United States of America
PG  - 6472--6477
VI  - 101
IP  - 17
4099  - http://www.pnas.org/content/101/17/6472.short
4100  - http://www.pnas.org/content/101/17/6472.full
SO  - Proc Natl Acad Sci U S A2004 Apr 27; 101
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.