A “Weird” Mitochondrial Fatty Acid Oxidation as a Metabolic “Secret” of Cancer

Figure 5

Antagonism between mFAO and glycolysis and accumulation of acetyl-CoA from fatty acid oxidation (adapted according to De Oliveira and Liesa [70]). Overactivated mitochondrial β-oxidation inhibits glycolysis and may also suppress the Krebs cycle. The main consequences are increased mitochondrial ratios of NADH/NAD⁺, acetyl-CoA/CoA, ATP/ADP, as well as citrate accumulation in the mitochondria. The green arrows indicated the expressed pathway. The gray arrows indicate the suppressed pathway. The red blunt ends indicate the inhibition of a particular enzyme. ACC1 and ACC2: acetyl-CoA carboxylases 1 and 2; ACLY: ATP citrate lyase; AMPK: 5AMP-activated protein kinase (dephosphorylated state); CIC: mitochondrial citrate carrier; CTP1 and CTP2: carnitine palmitoyl transferases 1 and 2; F6P: fructose-6-phosphate/fructose-1,6-bisphosphate; G6P: glucose-6-phosphate; GAP: glyceraldehyde-3-phosphate; a-KG: a-ketoglutarate; MCD: malonyl-CoA decarboxylase; MPC: mitochondrial pyruvate carrier; OAA: oxaloacetate; PDH: pyruvate dehydrogenase; PC: pyruvate carboxylase; PFK1: phosphofructokinase-1; PEP: phosphoenolpyruvate; PK: pyruvate kinase; Succ: succinate.