Fig. 3. Acetyl-CoA from p53-mediated peroxisomal FAO regulates ATIC activity.
a A schematic diagram of the mitochondrial and peroxisomal FAO in mammalian cells and cytosolic acetyl-coA production. ACLY, ATP-citrate lyase; ACSS2, Acyl-CoA synthetase short-chain family members 2; ACOX1, Acyl-CoA oxidase 1. b Cytosolic acetyl-CoA measurement in the tumor tissues from CRC mouse model and HCT116 cells, n = 3 or 5. c Docosanoic-d43 acid isotope profiling analysis revealed acetyl-CoA (m + 1) metabolism is suppressed when p53 deletion in HCT116 and MEFs, n = 3. d Docosanoic-d43 acid and palmitate (13C16) isotope profiling analysis was performed in the HCT116 cells, n = 3. e Western blot analysis of ACLY, ACSS2, and ACOX1 expression in n CRC tumors from Trp53fl/fl and VP mice, n = 3. f Top acetylation of metabolic enzymes that are significantly associated with p53 KO. g A schematic diagram of the purine biosynthesis pathway. h Lysine acetylation of endogenous ATIC was analyzed in CRC tumors from Trp53fl/fl and VP mice by immunoprecipitation using an ATIC antibody, followed by western blot analysis using AcK antibody. i Effect of p53 deletion on ATIC activity in CRC tumors from CRC mouse model, HCT116 and MEFs, n = 3 or 6. j Relative purine nucleotide levels were analyzed by LC-MS/MS in CRC tumors from Trp53fl/fl and VP mice and normalized to per mg tissue, n = 3. Data were presented as mean ± SD. ns, non-significant, P > 0.05.