The nonautophagic functions of autophagy-related proteins

Abstract

ATG: autophagy related; BECN1: beclin 1; cAMP: cyclic adenosine monophosphate; dsDNA: double-stranded DNA; EMT: epithelial-mesenchymal transition; IFN: interferon; ISCs: intestinal stem cells; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK/JNK: mitogen-activated protein kinase/c-Jun N-terminal kinases; MTOR: mechanistic target of rapamycin kinase; STING1: stimulator of interferon response cGAMP interactor 1; UVRAG: UV radiation resistance associated; VPS: vacuolar protein sorting.

Keywords: autophagy-related proteins; cargo transport; cell growth and senescence; metabolic homeostasis; nonautophagic functions; signal transduction.

Figure 1.

Overview of autophagy. The PIK3C3/VPS34 and ULK1 complexes are involved in the initiation of autophagy. ATG4 cleaves LC3 and participates in LC3 lipidation. ATG7 contributes to two ubiquitin-like processes, which are formed by the ATG12–ATG5 system and LC3 system, respectively. Both ubiquitin-like systems are involved in the elongation and maturation of autophagosomes, which are fused with lysosomes and delivering their encapsulated contents for degradation ultimately.

Figure 2.

Overview of the nonautophagic functions of ATGs. The ULK1-ATG13-RB1CC1/FIP200-ATG101 complex activates autophagy, the ATG12–ATG5-ATG16L1 complex contributes to the extension of autophagic vesicles, and LC3 is involved the formation of autophagosomes. However, ATGs function in many nonautophagic physiological roles. For instance, ULK1 is involved in neurodevelopment as well as cell and organ development; UVRAG regulates genomic stability; AMBRA1 is involved in cell growth and proliferation; ATG4 regulates cell senescence and cell death; ATG5 regulates the immune response; BECN1 affects the cell cycle; ATG7 regulates gene transcription; LC3 is involved in cargo transport and phagocytosis; and ATG16L1 is involved in the regulation of cell metabolic homeostasis.