1. Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis.
- Author
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Stempels FC, Janssens MH, Ter Beest M, Mesman RJ, Revelo NH, Ioannidis M, and van den Bogaart G
- Subjects
- Autophagosomes metabolism, Autophagy genetics, Cell Differentiation, Chloroquine pharmacology, Class III Phosphatidylinositol 3-Kinases antagonists & inhibitors, Class III Phosphatidylinositol 3-Kinases genetics, Class III Phosphatidylinositol 3-Kinases metabolism, Dendritic Cells cytology, Dendritic Cells metabolism, Endosomes drug effects, Endosomes metabolism, Gene Expression Regulation, Humans, Lysosomes drug effects, Lysosomes metabolism, Macrolides pharmacology, Microtubule-Associated Proteins antagonists & inhibitors, Microtubule-Associated Proteins genetics, Microtubule-Associated Proteins metabolism, Monocytes cytology, Monocytes metabolism, Phagocytosis genetics, Phagosomes drug effects, Phagosomes metabolism, Primary Cell Culture, Proteasome Endopeptidase Complex metabolism, Pyridines pharmacology, Pyrimidinones pharmacology, Thiophenes pharmacology, Zymosan metabolism, Autophagosomes drug effects, Autophagy drug effects, Dendritic Cells drug effects, Phagocytosis drug effects, Proteasome Endopeptidase Complex drug effects
- Abstract
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., (© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2022
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