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

Figure 3

(a) Regulation of FAS and mFAO by AMPK at normal or high ATP/ADP ratio. In this case, AMPK is in inactive state, ACC1 and ACC2 are active, and the accumulated malonyl-CoA inhibits the β-oxidation of fatty acids in the mitochondria by suppressing CPT1 and CPT2 activity. (b) Regulation of FAS and mFAO by AMPK at low ATP/ADP ratio. In this case, AMPK is in an active state (AMPK-P), ACC1 and ACC2 are deactivated, malonyl-CoA is removed by activated MCD, which eliminates the inhibition of CPT1 and CPT2 and activates the β-oxidation of fatty acids 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. The red arrows indicated the activation 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.

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