Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis

Femmy C Stempels, Maaike H Janssens, Martin Ter Beest, Rob J Mesman, Natalia H Revelo, Melina Ioannidis, Geert van den Bogaart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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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.

Original languageEnglish
Article number14280
Pages (from-to)491-509
Number of pages19
JournalFEBS Letters
Issue number4
Early online date10-Jan-2022
Publication statusPublished - Feb-2022

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