Metabolic axis of autophagy: A key player in tumor maintenance and opportunities for therapeutic exploitation

Figure 1 The macroautophagy pathway and recycling of macromolecules. AKT: Protein kinase B; AMPK: Adenosine monophosphate-activated protein kinase; ATG: Autophagy-related protein; ATP: Adenosine triphosphate; LC3: Light chain 3; mTORC: Mechanistic target of rapamycin complex; PI3KC1: Phosphatidylinositol 3-kinase complex 1; PE: Phosphatidylethanolamine; ULK1: Unc-51 like autophagy activating kinase 1.

Figure 2 Regulation of autophagy by glucose metabolism. AMPK: Adenosine monophosphate-activated protein kinase; ATP: Adenosine triphosphate; FBP: Fructose 1,6-bisphosphate; LKB1: Liver kinase B1; mTORC: Mechanistic target of rapamycin complex; TRPV: Transient receptor potential channel subfamily V; ULK: Unc-51 like autophagy activating kinase.

Figure 3 Acetyl coenzyme A, nicotinamide adenine dinucleotide (plus) hydrogen/nicotinamide adenine dinucleotide⁺ in autophagy regulation. Acetyl CoA: Acetyl coenzyme A; ATG: Autophagy-related protein; LC3: Light chain 3; NAD⁺: Nicotinamide adenine dinucleotide⁺; VPS: Vacuolar protein sorting.

Figure 4 Regulation of autophagy by amino acid metabolism. AMPK: Adenosine monophosphate-activated protein kinase; ATF: Activating transcription factor; ATP: Adenosine triphosphate; elf2α: Eukaryotic initiation factor-2 alpha; tRNA: Transfer RNA; ULK: Unc-51 like autophagy activating kinase.

Figure 5 Regulation of autophagy by lipid metabolism. JNK: C-Jun N-terminal protein kinase; PKC: Protein kinase C; ROS: Reactive oxygen species; SCD: Stearoyl-coenzyme A desaturase.

Figure 6 Two different therapeutic approaches to target tumor cells. A: Differential stress resistance; B: Differential stress sensitization. CRMs: Caloric restriction mimetics; FMD: Fasting mimicking diets; STF: Short-term fasting.