Core autophagy machinery (ATG machinery) (ATG machinery)

The core autophagy machinery is a conserved set of proteins responsible for the initiation, nucleation, and expansion of the autophagosome, a double-membrane vesicle that delivers cytoplasmic material to the lysosome for degradation (Mizushima et al., 2011, Nature). This machinery is composed of several functional modules, including the ULK1/ATG1 kinase complex, the Class III PI3K (VPS34) complex, and the ATG12 and LC3/ATG8 conjugation systems (Galluzzi et al., 2017, EMBO J). These proteins work in a coordinated fashion to maintain cellular homeostasis by removing damaged organelles, protein aggregates, and intracellular pathogens (Levine & Kroemer, 2019, Cell). Dysregulation of the core autophagy machinery is implicated in a wide range of diseases, including neurodegeneration, where impaired clearance of toxic proteins occurs, and cancer, where autophagy can either suppress tumor initiation or promote the survival of established tumors (Kimmelman & White, 2017, Genes Dev). Therapeutic targeting of this machinery involves the use of small molecule inhibitors of ULK1 or VPS34 to sensitize cancer cells, or the use of activators to enhance the clearance of pathogenic aggregates in neurodegenerative conditions (Levy et al., 2017, Nat Rev Cancer). Monitoring the efficacy of such treatments often relies on measuring the conversion of LC3-I to LC3-II or the degradation of the cargo adapter p62/SQSTM1 (Klionsky et al., 2021, Autophagy).

Other names

Autophagy-related proteinsATG systemMacroautophagy machineryAutophagosome formation machinery

Modulation of autophagosome formation and maturation through the inhibition or activation of key enzymatic components such as the ULK1 kinase complex and the VPS34 lipid kinase complex, or by disrupting the fusion of autophagosomes with lysosomes.