Autophagy (macroautophagy)

Category: cell_death

Overview

Cellular self-eating — bulk degradation of cytoplasmic content via autophagosome → lysosome fusion. Regulated by mTORC1 (active mTORC1 INHIBITS autophagy; nutrient deprivation / rapamycin / metformin via AMPK activates it). Initiation: ULK1 complex. Nucleation: PI3K complex (Beclin-1 / VPS34). Elongation: ATG12-ATG5 conjugation + LC3 (MAP1LC3B) lipidation to PE on autophagosome membrane. Cargo capture (selective autophagy uses adaptors: p62/SQSTM1 for ubiquitinated cargo; NIX for mitochondria = mitophagy; nuclear/ER-phagy variants). Fusion with lysosome → autolysosome → cargo degraded by lysosomal hydrolases. Chloroquine + hydroxychloroquine inhibit autophagosome-lysosome fusion (basis for some cancer trial uses + part of antimalarial mechanism).

Organ Systems

Pathway Steps

Known Modulators