A model for the generation of basal autophagy and its coupling to stimulated autophagy.

<p>In fat body tissue, endocytic cell-compartment contains Rab5-positive vesicles issued partly by the activity of Vap/Spri modules. Here, the RasGAP homolog Vap (<i>Vacuolar Peduncle)</i>, negatively regulates the Rab5-GEF partner, Spri <i>(Sprint)</i>. Autophagy competent Rab5-vesicles drive nucleation of pre-autophagosome structures evolving into phagophores at multiple ER sites called omegasomes. This sets the foundation of the double-layered membranes of the autophagosome organelles. Rab5-vesicles “competence” presumably involves the recruitment or activation of proautophagy-competent Vps34 complexes (or Vps34-complex I) and translocation to omegasomes, ending in a local stimulation of PI(3)P synthesis and nucleation of proportionate PAS and phagophore components [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0209759#pone.0209759.ref076" target="_blank">76</a>] (i.e. higher PI(3)P synthesis promotes larger phagophores; see text). In normal fed cells, microscopic autophagosomes are manufactured from extant phagophores and these assume a basal autophagy rate (black arrow downward). On starvation, Rab5-vesicle density is increased (dashed grey arrow) causing further phagophore inflation, which is modeled on its extant architecture. Starvation-induced autophagosome size is therefore a reflection of fed-cell phagophore size. The parallel formation of endosomal membranes is not represented.</p>