ATG9 and ATG2 as lipid regulators linking cell recycling and vesicle release

Loss of the proteins ATG9A or ATG2A/B leads to increased secretion of small extracellular vesicles during lysosomal inhibition.

• Cells without ATG9A or ATG2A/B release more small extracellular vesicles (sEVs) when lysosomes are inhibited.
• These sEVs have lower levels of microtubule-associated protein 1A/1B-light chain 3 (LC3) and canonical autophagy cargo receptors.
• Impaired formation of amphisomes is observed in cells lacking ATG9A or ATG2A/B.
• Extensive remodeling of the cellular lipid composition occurs in the absence of these proteins.
• ATG9A and ATG2A/B may help regulate the distribution of membranes and cargo between autophagy and endosomal secretion.

Simplified