The estrogen-related receptor α (ERRα) functions in PPARγ coactivator 1α (PGC-1α)-induced mitochondrial biogenesis

摘要

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 ERRa is an effector of the transcriptional coactivator PGC-1α [peroxisome proliferator-acti-vated receptor y (PPARy) coactivator 1α], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Inhibition of ERRa 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 ERRa is sufficient to elicit both responses. ERRa binding sites are present in the transcriptional control regions of ERRa/PGC-1α-induced genes and contribute to the transcriptional response to PGC-1α. The ERRa-regulated genes described here have been reported to be expressed at reduced levels in humans that are insulin-resistant. Thus, changes in ERRa activity could be linked to pathological changes in metabolic disease, such as diabetes.