Autophagy in Macrophages: Impacting Inflammation and Bacterial Infection
Figure 1
(a) The general scheme of autophagic process is shown. Autophagy is defined as the sequestration of substrates into double-bilayer membrane vesicles termed autophagosomes for degradation. The autophagic process starts with the formation of isolation membrane (phagophore) that originates from various intracellular membrane sources. Initiation of the isolation membrane is followed by elongation and closure leading to a complete autophagosome that surrounds the cargo. The fusion of lysosomes with autophagosomes causes the formation of autolysosomes, where autophagic substrates are exposed to hydrolytic interior of lysosome resulting in their degradation. (b) The molecular representation of autophagy initiation is shown at phosphatidylinositol-3-phosphate- (PtdIns3P-) positive membrane structures named “omegasomes.” The induction of autophagy translocates ULK1 complex to the endoplasmic reticulum leading to activation of the PtdIns3P kinase (VPS34/Beclin-1/ATG14L) complex. VPS34-derived PtdIns3P recruits double FYVE-containing protein 1 (DFCP1/ZFYVE1) and WD-repeat protein interacting with phosphoinositides (WIPIs) to the outer membrane of autophagosomes causes the association of the ATG5/ATG12 conjugate with ATG16L1. The ATG5/ATG12/ATG16L1 complex then adds phosphatidylethanolamine group to the C-terminus of the LC3 protein promoting the elongation of isolation membrane.
