Figure 1.

The autophagy pathway and its regulation. The autophagy pathway proceeds through a series of stages, including nucleation of the autophagic vesicle, elongation and closure of the autophagosome membrane to envelop cytoplasmic constituents, docking of the autophagosome with the lysosome, and degradation of the cytoplasmic material inside the autophagosome. Vesicle nucleation depends on a class III PI(3)K complex that contains various proteins (in light yellow box at right), as well as additional proteins that regulate the activity of this complex (such as rubicon, UVRAG, Ambra-1 and Bif-1). Vesicle elongation and completion involves the activity of two ubiquitin-like conjugation systems (light blue box at right). The autophagy pathway is positively regulated (green box at left) and negatively regulated (red box at left) by diverse environmental and immunological signals. TNF, tumor necrosis factor; PE, phosphatidylethanolamine; Gly, glycine; E1 and E2, ligases for ubiquitin-like conjugation systems.