期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：17
页码：6472-6477
DOI：10.1073/pnas.0308686101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Estrogen-related receptor {alpha} (ERR{alpha}) is one of the first orphan nuclear receptors to be identified, yet its physiological functions are still unclear. We show here that ERR{alpha} is an effector of the transcriptional coactivator PGC-1{alpha} [peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) coactivator 1{alpha}], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Inhibition of ERR{alpha} compromises the ability of PGC-1{alpha} to induce the expression of genes encoding mitochondrial proteins and to increase mitochondrial DNA content. A constitutively active form of ERR{alpha} is sufficient to elicit both responses. ERR{alpha} binding sites are present in the transcriptional control regions of ERR{alpha}/PGC-1{alpha}-induced genes and contribute to the transcriptional response to PGC-1{alpha}. The ERR{alpha}-regulated genes described here have been reported to be expressed at reduced levels in humans that are insulin-resistant. Thus, changes in ERR{alpha} activity could be linked to pathological changes in metabolic disease, such as diabetes.
