Fig. 1

Overview of the autophagy-lysosomal degradation process. The initiation of autophagy is induced by a multiprotein complex consisting of ULK1/2, FIP200, ATG13, ATG17 and ATG101, which integrates stress signals from mTOR, AMPK and MAPK. The nucleation phase is controlled by Beclin1/VPS34/UVRAG/ATG4L/Bif-1 complex, which is negatively regulated by the antiapoptotic protein Bcl-2/Bcl-XL via its BH3 domain. The ATG12/ATG5/ATG16 and LC3-II are two dominate factors in the elongation phase to drive phagophore expansion. E3 ligase-like ATG12/ATG5/ATG16 multimeric complex is formed by the interaction of those proteins under the action of ligase E1 ATG7 and ligase E2 ATG10, and mediated membrane binding. LC3-II is from a cytosolic form of LC3-I by conjugating phosphatidylethanolamine (PE), which is catalyzed by ligase E1 ATG7 and ligase E2 ATG3, and then LC3-II is inserted into both outer and inner membranes of the growing phagophore. LC3-I is derived from pro-LC3 by ATG4 proteolytic cleavage to expose a C-terminal glycine and then conjugate PE. In the docking and fusion phase, autolysosome is generated by the fusion of autophagosome and lysosome. Finally the cargo-containing membrane and cytoplasm compartments are degraded and the essential biomolecules are recycled. Autophagy attenuates the damage caused by tumor therapeutic drugs and then produces multidrug resistance (MDR)