Separation of the gluconeogenic and mitochondrial functions of pgc-1α through s6 kinase
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Separation of the gluconeogenic and mitochondrial functions of pgc-1α through s6 kinase. / Lustig, Y.; Ruas, J.L.; Estall, J.L.; Lo, J.C.; Devarakonda, S.; Laznik, D.; Choi, J.H.; Spiegelman, B.M.; Ono, H.; Olsen, J.V.
In: Genes & Development, Vol. 25, No. 12, 15.06.2011, p. 1232-1244.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Separation of the gluconeogenic and mitochondrial functions of pgc-1α through s6 kinase
AU - Lustig, Y.
AU - Ruas, J.L.
AU - Estall, J.L.
AU - Lo, J.C.
AU - Devarakonda, S.
AU - Laznik, D.
AU - Choi, J.H.
AU - Spiegelman, B.M.
AU - Ono, H.
AU - Olsen, J.V.
PY - 2011/6/15
Y1 - 2011/6/15
N2 - 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. © 2011 by Cold Spring Harbor Laboratory Press.
AB - 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. © 2011 by Cold Spring Harbor Laboratory Press.
UR - http://www.scopus.com/inward/record.url?scp=79959635928&partnerID=8YFLogxK
U2 - 10.1101/gad.2054711
DO - 10.1101/gad.2054711
M3 - Journal article
C2 - 21646374
VL - 25
SP - 1232
EP - 1244
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
IS - 12
ER -
ID: 33754079