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Lysosome fusion, the fusion of autophagosomes with lysosomes, is a critical late-stage event in the autophagy pathway. Inhibition of this fusion step effectively blocks the completion of autophagic flux and leads to accumulation of undegraded material within cells. The fusion process requires SNARE proteins (Stx17, SNAP29, VAMP8), RAB7 GTPase, and the HOPS complex. Several small molecules, such as EACC, chloroquine, and bafilomycin A1, inhibit this step, leading to accumulation of autophagosomes and blockage in degradation/recycling pathways. Improper control over this step has been linked to various human disorders including neurodegenerative diseases and cancer. Targeted inhibition can sensitize cancer cells by preventing their ability to recycle nutrients under stress conditions.
Blocks the fusion of autophagosomes with lysosomes, preventing the degradation of cargo and completion of the autophagy pathway.
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