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Choi, Jang Hyun
Lab of Diabetes and Metabolism (LDM)
Research Interests
  • Diabetes, Metabolic Disorders, PPARg, Gene Regulation, Anti-Diabetic Drug

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Separation of the gluconeogenic and mitochondrial functions of PGC-1 alpha through S6 kinase

Cited 29 times inthomson ciCited 27 times inthomson ci
Title
Separation of the gluconeogenic and mitochondrial functions of PGC-1 alpha through S6 kinase
Author
Lustig, YanivRuas, Jorge L.Estall, Jennifer L.Lo, James C.Devarakonda, SrikripaLaznik, DinaChoi, Jang HyunOno, HirakuOlsen, Jesper V.Spiegelman, Bruce M.
Issue Date
2011-06
Publisher
COLD SPRING HARBOR LAB PRESS
Citation
GENES & DEVELOPMENT, v.25, no.12, pp.1232 - 1244
Abstract
PGC-1α is a transcriptional coactivator that powerfully regulates many pathways linked to energy homeostasis. Specifically, PGC-1α controls mitochondrial biogenesis in most tissues but also initiates important tissue-specific functions, including fiber type switching in skeletal muscle and gluconeogenesis and fatty acid oxidation in the liver. We show here that S6 kinase, activated in the liver upon feeding, can phosphorylate PGC-1α directly on two sites within its arginine/serine-rich (RS) domain. This phosphorylation significantly attenuates the ability of PGC-1α to turn on genes of gluconeogenesis in cultured hepatocytes and in vivo, while leaving the functions of PGC-1α as an activator of mitochondrial and fatty acid oxidation genes completely intact. These phosphorylations interfere with the ability of PGC-1α to bind to HNF4α, a transcription factor required for gluconeogenesis, while leaving undisturbed the interactions of PGC-1α with ERRα and PPARα, factors important for mitochondrial biogenesis and fatty acid oxidation. These data illustrate that S6 kinase can modify PGC 1α and thus allow molecular dissection of its functions, providing metabolic flexibility needed for dietary adaptation.
URI
https://scholarworks.unist.ac.kr/handle/201301/7223
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=79959635928
DOI
10.1101/gad.2054711
ISSN
0890-9369
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BIO_Journal Papers
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