Premium
Novel and conventional inhibitors of canonical autophagy differently affect LC3‐associated phagocytosis
Author(s) -
Stempels Femmy C.,
Janssens Maaike H.,
Beest Martin,
Mesman Rob J.,
Revelo Natalia H.,
Ioannidis Melina,
den Bogaart Geert
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14280
Subject(s) - autophagy , bafilomycin , chloroquine , phagosome , phagocytosis , endosome , microbiology and biotechnology , lysosome , chemistry , lipid bilayer fusion , proteasome , membrane , biology , biochemistry , intracellular , immunology , enzyme , apoptosis , malaria
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.