雌激素相关受体α（ERRα）在过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）诱导的线粒体生物发生过程中发挥作用。
The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis.
作者信息
Schreiber Sylvia N, Emter Roger, Hock M Benjamin, Knutti Darko, Cardenas Jessica, Podvinec Michael, Oakeley Edward J, Kralli Anastasia
机构信息
Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
出版信息
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6472-7. doi: 10.1073/pnas.0308686101. Epub 2004 Apr 15.
Abstract
Estrogen-related receptor alpha (ERRalpha) is one of the first orphan nuclear receptors to be identified, yet its physiological functions are still unclear. We show here that ERRalpha is an effector of the transcriptional coactivator PGC-1alpha [peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Inhibition of ERRalpha compromises the ability of PGC-1alpha to induce the expression of genes encoding mitochondrial proteins and to increase mitochondrial DNA content. A constitutively active form of ERRalpha is sufficient to elicit both responses. ERRalpha binding sites are present in the transcriptional control regions of ERRalpha/PGC-1alpha-induced genes and contribute to the transcriptional response to PGC-1alpha. The ERRalpha-regulated genes described here have been reported to be expressed at reduced levels in humans that are insulin-resistant. Thus, changes in ERRalpha activity could be linked to pathological changes in metabolic disease, such as diabetes.
摘要
雌激素相关受体α（ERRα）是最早被鉴定出的孤儿核受体之一，但其生理功能仍不清楚。我们在此表明，ERRα是转录共激活因子PGC-1α[过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子1α]的效应器，并且它调节参与氧化磷酸化和线粒体生物发生的基因的表达。抑制ERRα会损害PGC-1α诱导线粒体蛋白编码基因表达和增加线粒体DNA含量的能力。ERRα的组成型活性形式足以引发这两种反应。ERRα结合位点存在于ERRα/PGC-1α诱导基因的转录控制区域，并有助于对PGC-1α的转录反应。此处描述的ERRα调节的基因据报道在胰岛素抵抗的人类中表达水平降低。因此，ERRα活性的变化可能与代谢疾病如糖尿病的病理变化有关。
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