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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Apr 27 2004|
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