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

• DOI: 10.1101/gad.2054711
• Publication Date: 2011-06-07T04:15:16Z
• Authors: Yaniv Lustig; Jorge L. Ruas; Jennifer L. Estall; James C. Lo; Srikripa Devarakonda; Dina Laznik; Jang Hyun Choi; Hiraku Ono; Jesper V. Olsen; Bruce M. Spiegelman
• Keywords: Gluconeogenesis; AMP-Activated Protein Kinase

PGC-1α is a transcriptional coactivator that powerfully regulates many pathways linked to energy homeostasis. Specifically, controls mitochondrial biogenesis in most tissues but also initiates important tissue-specific functions, including fiber type switching skeletal muscle and gluconeogenesis fatty acid oxidation the liver. We show here S6 kinase, activated liver upon feeding, can phosphorylate directly on two sites within its arginine/serine-rich (RS) domain. This phosphorylation significantly attenuates ability of turn genes cultured hepatocytes vivo, while leaving functions as an activator completely intact. These phosphorylations interfere with bind HNF4α, transcription factor required for gluconeogenesis, undisturbed interactions ERRα PPARα, factors oxidation. data illustrate kinase modify thus allow molecular dissection providing metabolic flexibility needed dietary adaptation.