Article (Scientific journals)
NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.
Yamamoto, Hiroyasu; Williams, Evan; Mouchiroud, Laurent et al.
2011In Cell, 147 (4), p. 827-39
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Keywords :
Animals; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics/metabolism; Gene Deletion; Gene Knockdown Techniques; Humans; Mice; Mitochondria, Muscle/metabolism; Muscle Development; Muscle, Skeletal/metabolism; Nuclear Receptor Co-Repressor 1/genetics/metabolism; PPAR delta/metabolism; PPAR-beta/metabolism; Physical Conditioning, Animal
Abstract :
[en] Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARbeta/delta, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.
Disciplines :
Genetics & genetic processes
Author, co-author :
Yamamoto, Hiroyasu
Williams, Evan  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Mouchiroud, Laurent
Canto, Carles
Fan, Weiwei
Downes, Michael
Heligon, Christophe
Barish, Grant D.
Desvergne, Beatrice
Evans, Ronald M.
Schoonjans, Kristina
Auwerx, Johan
External co-authors :
yes
Language :
English
Title :
NCoR1 is a conserved physiological modulator of muscle mass and oxidative function.
Publication date :
2011
Journal title :
Cell
ISSN :
1097-4172
Publisher :
Cell Press, United States - Massachusetts
Volume :
147
Issue :
4
Pages :
827-39
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2011 Elsevier Inc. All rights reserved.
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