AutophagosomLysosomSystem

AutophagosomLysosomSystem is the cellular pathway for degrading and recycling cytoplasmic material via autophagosomes that fuse with lysosomes. It encompasses macroautophagy and related selective autophagy processes, and serves as a major quality-control and energy-generation mechanism.

Initiation occurs under nutrient stress with ULK1 complex inhibited by mTORC1; autophagy-related (ATG) proteins reorganize membranes; PI3KC3 complex Beclin-1-Vps34 nucleates the phagophore; expansion uses ATG5-ATG12-ATG16L1, lipidation of LC3 to LC3-II that decorates the growing membrane and helps cargo recruitment via receptors such as p62/SQSTM1 and NBR1.

Closed autophagosome fuses with lysosome, mediated by SNAREs (e.g., syntaxin 17), Rab7, and the HOPS tethering complex; new compartment is autolysosome where lysosomal hydrolases degrade cargo; resulting macromolecules are recycled to the cytosol.

Regulated by energy status via AMPK activation and mTORC1 inhibition; supports turnover of damaged organelles (mitophagy, ER-phagy), protein aggregates, and pathogens (xenophagy); essential for development, immunity, and adaptation to starvation.

Dysregulation is linked to neurodegenerative diseases, cancer and infection; therapeutic strategies seek to induce or inhibit autophagy depending on disease context. Researchers monitor autophagic flux using LC3-II, p62, and imaging of autophagosomes versus autolysosomes.