Nutrient-dependent regulation of PGC-1α's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5

John E. Dominy, Yoonjin Lee, Zachary Gerhart-Hines, Pere Puigserver*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftReviewForskningpeer review

160 Citationer (Scopus)

Abstract

Mammals possess an intricate regulatory system for controlling flux through fuel utilization pathways in response to the dietary availability of particular macronutrients. Under fasting conditions, for instance, mammals initiate a whole body metabolic response that limits glucose utilization and favors fatty acid oxidation. Understanding the underlying mechanisms by which this process occurs will facilitate the development of new treatments for metabolic disorders such as type II diabetes and obesity. One of the recently identified components of the signal transduction pathway involved in metabolic reprogramming is PGC-1α. This transcriptional coactivator is able to coordinate the expression of a wide array of genes involved in glucose and fatty acid metabolism. The nutrient-mediated control of PGC-1α activity is tightly correlated with its acetylation state. In this review, we evaluate how the nutrient regulation of PGC-1α activity squares with the regulation of its acetylation state by the deacetylase Sirt1 and the acetyltransferase GCN5. We also propose an outline of additional experimental directives that will help to shed additional light on this very powerful transcriptional coactivator.

OriginalsprogEngelsk
TidsskriftBiochimica et Biophysica Acta - Proteins and Proteomics
Vol/bind1804
Udgave nummer8
Sider (fra-til)1676-1683
Antal sider8
ISSN1570-9639
DOI
StatusUdgivet - aug. 2010

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