Secretory autophagy during lysosome inhibition (SALI)

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• Autophagy and extracellular vesicle (EV) secretion converge at the endolysosome.
• Lysosome impairment disrupts autophagic degradation, but its effect on EV secretion is unclear.

Purpose of the Study:

• To investigate the impact of lysosome dysfunction on EV secretion.
• To characterize a novel secretory autophagy pathway termed SALI.

Main Methods:

• Investigated the role of autophagosome formation and RAB27A in the novel pathway.
• Analyzed the secretion of autophagy cargo receptors during lysosome inhibition.

Main Results:

• Discovered a novel pathway, SALI, where EVs/nanoparticles (EVPs) secrete autophagy cargo receptors when autophagosome maturation or lysosomal function is blocked.
• SALI requires functional autophagosome formation steps and the small GTPase RAB27A.
• Intracellular accumulation of cargo receptors disrupts cell signaling and quality control.

Conclusions:

• SALI acts as a failsafe mechanism to maintain protein and cellular homeostasis during impaired autophagy or lysosomal degradation.
• This pathway facilitates the extracellular removal of autophagy cargo receptors under stress conditions.
• Understanding SALI is crucial for comprehending cellular quality control and protein homeostasis.