Transcriptional coregulators: Fine-tuning metabolism

Laurent Mouchiroud, Lillian J. Eichner, Reuben J. Shaw*, Johan Auwerx

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

94 Scopus citations

Abstract

Metabolic homeostasis requires that cellular energy levels are adapted to environmental cues. This adaptation is largely regulated at the transcriptional level, through the interaction between transcription factors, coregulators, and the basal transcriptional machinery. Coregulators, which function as both metabolic sensors and transcriptional effectors, are ideally positioned to synchronize metabolic pathways to environmental stimuli. The balance between inhibitory actions of corepressors and stimulatory effects of coactivators enables the fine-tuning of metabolic processes. This tight regulation opens therapeutic opportunities to manage metabolic dysfunction by directing the activity of cofactors toward specific transcription factors, pathways, or cells/tissues, thereby restoring whole-body metabolic homeostasis.

Original languageEnglish (US)
Pages (from-to)26-40
Number of pages15
JournalCell Metabolism
Volume20
Issue number1
DOIs
StatePublished - Jul 1 2014
Externally publishedYes

Funding

J.A. holds the Nestl\u00E9 Chair in Energy Metabolism at EPFL. The work in the Auwerx laboratory is supported by the EPFL, the EU Ideas program (ERC-2008-AdG-23138), the NIH (R01HL106511-01A1 and R01AG043930), and the Swiss National Science Foundation (31003A-124713 and CRSII3-136201). R.J.S. is an Early Career Scientist in the Howard Hughes Medical Institute. Work in the Shaw laboratory is also supported by the NIH (R01DK080425 and P01CA120964) as well as by the Leona M. and Harry B. Helmsley Charitable Trust grant #2012-PG-MED002. L.J.E. was supported by a training grant (T32 CA009370) to the Salk Institute Center for Cancer Research (P30CA014195). The authors have no conflict of interest related to this work.

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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