TY - JOUR
T1 - Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis
AU - Stempels, Femmy C
AU - Janssens, Maaike H
AU - Ter Beest, Martin
AU - Mesman, Rob J
AU - Revelo, Natalia H
AU - Ioannidis, Melina
AU - van den Bogaart, Geert
N1 - Funding Information:
GvdB is funded by a Young Investigator Grant from the Human Frontier Science Program (HFSP; RGY0080/2018). GvdB has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 862137).
Publisher Copyright:
© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
U2 - 10.1002/1873-3468.14280
DO - 10.1002/1873-3468.14280
M3 - Article
C2 - 35007347
SN - 0014-5793
VL - 596
SP - 491
EP - 509
JO - FEBS Letters
JF - FEBS Letters
IS - 4
M1 - 14280
ER -