(A) Electron micrograph comparing the appearance of an autophagosome (1) versus autolysosome (2) with conventional lysosomes (Ly).
(B) A composite of autophagic membrane formation (schematic) with actual autophagosome from an electron micrograph. Three stages can be discerned by ultrastructural morphology: initiation (crescent membrane decorated on both ssides with Atg protein-lipid [Atg8-PE; known as LC3-II] and protein-protein conjugates [Atg12-Atg5, complexed with Atg16]), elongation (growth of isolation membrane) ending in its closure to form an autophagosome, and maturation that involves the formation of degradative autolysosomes through fusion of autophagosomes with lysosomal organelles (electron-dense granular material represents ribosomal degradation intermediates). All micrographs in (A) and (B) are courtesy of Eeva-Lisa Eskalinen (reproduced with permission)
(C) Two signaling systems control induction of autophagy: left, hVps34-Beclin 1; right, Tor-Atg1. Various signals and systems transmitting them that lead to autophagy activation are shown in smaller boxes. Rapamycin induces autophagy by inhibiting Tor, and some immune signals that are transmitted via TLR adapters MyD88 and TRIF or DAPK downstream of IFNγ lead to activation of Beclin 1 (complexed with the phosphatidylinositol 3 kinase hVps34) by its dissociation from Bcl-2. Note that starvation, a classical inducer of autophagy, affects both Bcl-2-Beclin 1 complex (via JNK1) and Tor activity. Th2 cytokines and many growth factors in general inhibit autophagy via Tor (or in the case of immunologically induced autophagy, e.g., by IFNγ, via Stat-6 downstream of IL-4/IL-13).
(D)Immunological inputsand outputs of autophagy. Xenophagy,autophagic Macrophage activation, additional terms, factors, and relationships are described in the text.