Autophagy pathway components (ATG pathway)

Autophagy is a highly conserved catabolic process where cells deliver cytoplasmic material, such as damaged organelles and misfolded proteins, to lysosomes for degradation and recycling (Mizushima & Komatsu, 2011). The autophagy pathway components include a series of autophagy-related (ATG) proteins that orchestrate the initiation, nucleation, and maturation of the double-membraned autophagosome (Galluzzi et al., 2017). Key regulatory complexes include the ULK1 kinase complex for initiation and the Class III PI3K (VPS34) complex for vesicle nucleation. This pathway is essential for maintaining cellular homeostasis, and its dysfunction is linked to neurodegeneration, metabolic disorders, and cancer (Levy et al., 2017). In oncology, autophagy acts as a double-edged sword, suppressing early tumor development but promoting the survival of established cancer cells under metabolic stress. Pharmacological modulation involves either induction via mTORC1 inhibitors like Rapamycin to clear toxic aggregates or inhibition using agents like Chloroquine to sensitize tumors to chemotherapy (Klionsky et al., 2021). Current drug development focuses on targeting specific ATG proteins to achieve more precise therapeutic outcomes with fewer systemic side effects.

Other names

Macroautophagy pathwayAutophagy-related proteinsATG protein systemCellular self-eating pathway

mTORC1 inhibition (induction), ULK1 inhibition, VPS34 inhibition, Lysosomal acidification inhibition, ATG4B inhibition