Ye 2011 J Biol Chem
Ye F, Lemieux H, Hoppel CL, Hanson RW, Hakimi P, Croniger CM, Puchowicz M, Anderson VE, Fujioka H, Stavnezer E (2011) Peroxisome proliferator-activated receptor Ξ³ (PPARΞ³) mediates a Ski-induced shift from glycolysis to oxidative energy metabolism. J Biol Chem 286:40013-24. |
Ye F, Lemieux H, Hoppel CL, Hanson RW, Hakimi P, Croniger CM, Puchowicz M, Anderson VE, Fujioka H, Stavnezer E (2011) J Biol Chem
Abstract: Over-expression of the Ski oncogene induces oncogenic transformation of chicken embryo fibroblasts (CEFs). However, unlike most other oncogene-transformed cells, Ski-transformed CEFs (Ski-CEFs) do not display the classical Warburg effect. On the contrary, Ski transformation reduced lactate production and glucose utilization in CEFs. Compared to CEFs, Ski-CEFs exhibited enhanced TCA cycle activity, fatty acid catabolism through Ξ²-oxidation, glutamate oxidation, oxygen consumption, as well as, increased numbers and mass of mitochondria. Interestingly, expression of PPARΞ³, a key transcription factor that regulates adipogenesis and lipid metabolism was dramatically elevated at both the mRNA and protein levels in Ski-CEFs. Accordingly, PPARΞ³ target genes that are involved in lipid uptake, transport and oxidation were also markedly up-regulated by Ski. Knocking down PPARΞ³ in Ski-CEFs by RNA interference reversed the elevated expression of these PPARΞ³ target genes, as well as the shift to oxidative metabolism and the increased mitochondrial biogenesis. Moreover, we found that Ski co-immunoprecipitates with PPARΞ³ and co-activates PPARΞ³-driven transcription. β’ Keywords: Chicken embryo fibroblasts (CEFs)
β’ O2k-Network Lab: US_OH_Cleveland_Hoppel_CL, CA_Edmonton_Lemieux_H
Labels: MiParea: Respiration, mt-Biogenesis;mt-density
Organism: Chicken
Tissue;cell: Fibroblast
Preparation: Intact cells
Regulation: Aerobic glycolysis Coupling state: ROUTINE
HRR: Oxygraph-2k