Autophagosome–lysosome fusion process

The autophagosome–lysosome fusion process is a key stage in macroautophagy, where mature double-membrane autophagosomes fuse with lysosomes to create autolysosomes, enabling lysosomal hydrolases to degrade sequestered cytoplasmic material. This step is regulated by multiple molecules, including small GTPases (notably RAB7), SNARE proteins (Syntaxin 17, SNAP29, VAMP8), various tethering complexes (e.g., HOPS complex), actin cytoskeleton, phosphoinositides, and additional factors (e.g., ATG14)[1][2][3][4][5]. Disruption of this fusion step impairs autophagic clearance, contributing to the pathogenesis of a range of human diseases, particularly neurodegeneration and cancer. Certain small molecules and drugs, such as EACC and bafilomycin A1, can experimentally or therapeutically target this process, though it is not a drug target in the traditional, molecule-specific sense. This entry is not a canonical therapeutic target as typically defined, but rather a crucial biological process composed of multiple molecular participants whose disruption or modulation impacts cellular and disease biology[2][5].

Other names

Autophagosome–lysosome fusionAutophagosome–endolysosome fusionAutolysosome formationAutophagic vesicle–lysosome fusion

Inhibition of SNARE-mediated membrane fusion. Lysosomal pH neutralization (impairs degradation post-fusion, sometimes also impairs fusion itself). Disruption of cytoskeletal trafficking leading to failed organelle apposition/fusion.