Autophagy in the nematode Caenorhabditis elegans. (A) The process of autophagy has been delineated by studies in yeast and mammalian cells. It is presumed that induction of autophagy begins with the activation of UNC-51, via loss of signaling from the C. elegans ortholog of the target of rapamycin (TOR), LET-363. (B) Autophagosome formation requires the integral protein ATG-9, thought to contribute membrane to the developing autophagosome. (C) Nucleation requires the class III phosphoinositide 3-kinase (PI3K) complex (BEC-1–VPS-34–ATG-14), which recruits downstream autophagy proteins to the isolation membranes (IMs) in mammals or preautophagosomal structure (PAS) in yeast, through the production of phosphatidylinositol 3-phosphate (PI3P; pale purple). (D) Two conjugation complexes (LGG-1 and ATG-12) are required for elongation of the IMs and completion of the developing autophagosome. LGG-1 conjugated to phosphatidylethanolamine (PE, red) binds to both the inner and outer membranes of the autophagosome. LGG-1 also has the ability to bind to autophagic adaptor proteins, such as SQST-1 (encoded by T12G3.1), which bind to polyubiquitylated aggregates. (E) The complete autophagosome eventually fuses with the lysosome (depicted in a red circle), leading to the degradation of cargo within the autophagosome.