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PMID: 15087503 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 17 ·2004-04-27 ·Pages 6472-7

Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A

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.

MeSH Terms
Animals COS Cells Cytochromes c/genetics,metabolism Gene Expression Regulation/physiology Mitochondria/physiology Oxidative Phosphorylation Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Promoter Regions, Genetic Receptors, Cytoplasmic and Nuclear/physiology Receptors, Estrogen/physiology Trans-Activators/physiology Transcription Factors
Chemicals
ERRalpha estrogen-related receptor Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Ppargc1a protein, mouse Receptors, Cytoplasmic and Nuclear Receptors, Estrogen Trans-Activators Transcription Factors Cytochromes c
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Schreiber Sylvia N
Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
Emter Roger
Hock M Benjamin
Knutti Darko
Cardenas Jessica
Podvinec Michael
Oakeley Edward J
Kralli Anastasia
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0308686101
Published
2004-04-27
Epub
2004-00-15
Pages
6472-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC404069
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0308686101 PMC Full Text View journal details
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