biostudies-literatureDebnath JNIA NIH HHSThe Mark Foundation for Cancer ResearchSamuel Waxman Cancer Research FoundationUCSF QB3 Calico Longevity FellowshipGovernment of CanadaNCI NIH HHSNIHCancer Research Society Scholarship for Next Generation of Scientists2498-2499https://www.ebi.ac.uk/biostudies/studies/S-EPMC9542525biostudies-literatureUnknown18(10)Both macroautophagy/autophagy and extracellular vesicle (EV) secretion pathways converge upon the endolysosome system. Although lysosome impairment leads to defects in autophagic degradation, the impact of such dysfunction on EV secretion remains poorly understood. Recently, we uncovered a novel secretory autophagy pathway that employs EVs and nanoparticles (EVPs) for the secretion of autophagy cargo receptors outside the cell when either autophagosome maturation or lysosomal function is blocked. We term this process secretory autophagy during lysosome inhibition (SALI). SALI functionally requires multiple steps in classical autophagosome formation and the small GTPase RAB27A. Because the intracellular accumulation of autophagy cargo receptors perturbs cell signaling and quality control paAutophagySecretory autophagy during lysosome inhibition (SALI).PMC954252522805R01 CA126792R21 CA201849R01 AG057462R01 CA213775CA201849201409BPF-335868Debnath JLeidal AMfalseSecretory autophagy during lysosome inhibition (SALI).Both macroautophagy/autophagy and extracellular vesicle (EV) secretion pathways converge upon the endolysosome system. Although lysosome impairment leads to defects in autophagic degradation, the impact of such dysfunction on EV secretion remains poorly understood. Recently, we uncovered a novel secretory autophagy pathway that employs EVs and nanoparticles (EVPs) for the secretion of autophagy cargo receptors outside the cell when either autophagosome maturation or lysosomal function is blocked. We term this process secretory autophagy during lysosome inhibition (SALI). SALI functionally requires multiple steps in classical autophagosome formation and the small GTPase RAB27A. Because the intracellular accumulation of autophagy cargo receptors perturbs cell signaling and quality control pa2022-01-01T00:00:00Z2022 Oct2025-04-22T21:12:22.124Z2025-04-22T21:12:22.124ZS-EPMC95425253578636710.1080/15548627.2022.2095788