Figure 1

A schematic summary of the autophagy machinery. (1) The nucleation of phagophore membranes (pre-autophagosomal structures or isolation membrane): In nutrient rich condition, the mTORC1 kinase associates with the ULK1/2 complex to inhibit the initiation of autophagy. Under growth factor deprivation or nutrient starvation, energy sensor AMPK suppresses the activity of mTORC1 and activates the ULK1/2 complex which is essential for the induction of autophagy. The ULK1/2 complex likely recruits the Vps34-Beclin-1 complex to the site of autophagosome generation. (2) The formation of autophagosomes: Two ubiquitin-like proteins, Atg12 and LC3, are involved in the formation of enclosed double-membrane vesicles (autophagosomes) in order to sequester cytoplasmic material. Atg12 is conjugated with Atg5 by Atg7 (E1-like ubiquitin activating enzyme) and Atg10 (E2-like ubiquitin conjugating enzyme), which then form a complex with Atg16L1; this complex (E3-like ubiquitin ligase) works with Atg7 (E1) and Atg3 (E2) to conjugate LC3-I with phosphatidylethanolamine (PE), to create a form termed LC3-II, which is specifically located on autophagosome structures. (3) The maturation of autophagosomes: Autophagosomes are sequentially fused with endosomes and lysosomes to form autolysosomes. The lysosomal hydrolases degrade eventually the content of autophagosomes. To date, Vps34-Beclin-1 complex, UVRAG, SNARE, ESCRT-III, Rab7, HSP70 and TECPR1 have been identified to be involved in autophagosome-lysosome fusion. Rubicon protein may serve as a suppressor of autophagosome maturation by interacting with VPS34-Beclin-1 complex.