Nutrient-dependent regulation of PGC-1α's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5
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Nutrient-dependent regulation of PGC-1α's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. / Dominy, John E.; Lee, Yoonjin; Gerhart-Hines, Zachary; Puigserver, Pere.
In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1804, No. 8, 08.2010, p. 1676-1683.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - Nutrient-dependent regulation of PGC-1α's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5
AU - Dominy, John E.
AU - Lee, Yoonjin
AU - Gerhart-Hines, Zachary
AU - Puigserver, Pere
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - Acetylation
KW - GCN5
KW - PGC-1α
KW - Sirt1
UR - http://www.scopus.com/inward/record.url?scp=77953292242&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2009.11.023
DO - 10.1016/j.bbapap.2009.11.023
M3 - Review
C2 - 20005308
AN - SCOPUS:77953292242
VL - 1804
SP - 1676
EP - 1683
JO - B B A - Proteins and Proteomics
JF - B B A - Proteins and Proteomics
SN - 1570-9639
IS - 8
ER -
ID: 347795625