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

Autor: Stempels FC; Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands., Janssens MH; Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands., Ter Beest M; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Mesman RJ; Department of Microbiology, RIBES, Faculty of Science, Radboud University Nijmegen, The Netherlands., Revelo NH; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Ioannidis M; Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands., van den Bogaart G; Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands.; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2022 Feb; Vol. 596 (4), pp. 491-509. Date of Electronic Publication: 2022 Jan 21.
DOI: 10.1002/1873-3468.14280
Abstrakt: 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.)
Databáze: MEDLINE
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