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

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

LC3-associated phagocytosis: a sorting mechanism for ubiquitinated membrane proteins?

The process of LC3-associated phagocytosis (LAP) combines elements of phagocytosis and autophagy. LAP is involved in clearance of pathogens and cell debris, antigen presentation, and immune signaling. However, the mechanistic role of LAP is incompletely understood. Based on observations from our recent study, we propose that LAP might serve as a sorting mechanism to cluster proteins destined for degradation into discrete domains of the phagosomal membrane