Which statement about the autophagic pathway is TRUE?
Macroautophagy major lysosome-dependent self-digestion pathway induced by starvation mTORC1 inhibition ER stress damaged organelles pathogen invasion critical homeostasis survival. Initiation involves nutrient sensor ULK1 complex phosphorylating Beclin-1-Vps34 complex generating PI3P enriched omegasome ER subdomain recruiting WIPI ATG2-ATG9 vesicles building isolation membrane phagophore expanding cup. Elongation via two ubiquitin-like systems ATG12-ATG5-ATG16L1 acting E3 ligase LC3/GABARAP lipidation phosphatidylethanolamine marks completed autophagosome double-membrane 0.5-1.5 micron capturing cytoplasmic cargo. For degradation autophagosome fuses late endosomes forming hybrid amphisome bearing Rab7 then lysosomes mediated trans-SNARE STX17-SNAP29-VAMP8 tether HOPS requiring activated Rab7 PLEKHM1. Fusion requires acidic pH active V-ATPase proton pump generating gradient. Bafilomycin A1 macrolide binds V0 c subunit V-ATPase inhibiting proton translocation raising lysosomal pH 4.5 to 6 blocking autophagosome-lysosome fusion degrading activity; LC3-II p62 accumulate demonstrating flux blockade standard assay widely used. Autophagosomes originate mainly ER ERGIC recycling endosomes mitochondria-associated membranes ATG9 vesicles not solely mitochondrial membranes; hydrolases cathepsins indispensable degradation; mammalian cells exhibit constitutive basal inducible autophagy.
Ref: Klionsky et al., Autophagy Guidelines, Autophagy 2021: Bafilomycin inhibits autophagosome-lysosome fusion.