Figure 4.

Role of p53 in Cancer Metabolism. In cells, p53 controls mitochondrial oxidative phosphorylation, glycolysis, glutaminolysis, and fatty acid oxidation. To preserve mitochondrial integrity and increase oxidative phosphorylation, p53 transcriptionally stimulates the synthesis Of Cytochrome C Oxidase 2 (SCO2), Apoptosis-inducing Factor (AIF), and p53-controlled ribonucleotide reductase (p53R2), and physically interacts with mtDNA Poly. p53 inhibits glucose absorption through direct suppression of GLUT 1 and 4 transcription and indirect repression of GLUT 3 expression. p53 inhibits glycolysis via adversely regulating phosphoglycerate mutase (PGM) at the protein level and transcriptionally inducing TIGAR and Parkin. PDH, which converts pyruvate to acetyl-CoA, is favorably regulated by Parkin. p53 suppresses the production of PDK2, which phosphorylates and inhibits the function of PDH. Glutaminase 2 (GLS2) catalyzes the hydrolysis of glutamine to glutamate and is induced by p53. This can then be transformed into α-KG. GLS2 enhances the TCA cycle and oxidative phosphorylation by raising α-KG levels. p53 physically interacts with G6PD to inhibit its activity, hence inhibiting PPP, a crucial mechanism for nucleotide synthesis and NADPH generation. p53 promotes fatty acid oxidation by inducing the expression of Guanidinoacetate methyltransferase deficiency (GAMT) and Lipin1. Fatty acid oxidation helps the maintenance of the TCA cycle and mitochondrial oxidative phosphorylation by generating acetyl-CoA.