Journal article Open Access
Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis
Stempels, Femmy C.; Janssens, Maaike H.; ter Beest, Martin; Mesman, Rob J.; Revelo, Natalia H.; Ioannidis, Melina; van den Bogaart, Geert
In autophagy, LC3-positive autophagophores fuse and encapsulate the autophagic cargo in a double-membrane structure. In contrast, lipidated LC3 (LC3-II) is directly formed at the phagosomal membrane in LC3-associated phagocytosis (LAP). In this study, we dissected the effects of autophagy inhibitors on LAP. SAR405, an inhibitor of VPS34, reduced levels of LC3-II and inhibited LAP. In contrast, the inhibitors of endosomal acidification bafilomycin A1 and chloroquine increased levels of LC3-II, due to reduced degradation in acidic lysosomes. However, while bafilomycin A1 inhibited LAP, chloroquine did not. Finally, EACC, which inhibits the fusion of autophagosomes with lysosomes, promoted LC3 degradation possibly by the proteasome. Targeting LAP with small molecule inhibitors is important given its emerging role in infectious and autoimmune diseases.
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Indexed in
- Publication date:
- December 6, 2021
- DOI:
-
- Keyword(s):
- LAP LC3-associated phagocytosis autophagy chloroquine bafilomycin A1 EACC SAR405
- Grants:
-
European Commission:
- POST-IT - Pathogen Oriented SNARE Trafficking for Immune Tailoring (862137)
- License (for files):
- Creative Commons Attribution 4.0 International