Figure 1.

Model of Cvt and autophagy transport to the vacuole. There are many shared mechanistic features for the two pathways. 1, Cvt complex formation: prAPI is synthesized in the cytosol, oligomerizes into a dodecamer, and assembles into a Cvt complex; 2, double-membrane vesicle formation: the Cvt complex is enwrapped by a membrane source which, upon expansion and completion, forms the double-membraned Cvt vesicle (Cvt pathway) or autophagosome (autophagy); 3, vesicle targeting to the vacuole: the double-membrane vesicle is then targeted to the vacuole followed by fusion with the vacuolar membrane and release of the inner vesicle, termed the Cvt body (Cvt pathway) or the autophagic body (autophagy), into the vacuolar lumen. Subsequent breakdown of the Cvt or autophagic body releases prAPI into the lumen where it is proteolytically processed, in a proteinase A-dependent manner, to mature API. Major differences between the pathways include the following: 1, cargo selectivity: the Cvt pathway is a selective process and the Cvt vesicles appear to exclude bulk cytosolic components as cargo. In contrast, autophagy is nonselective and autophagosomes carry bulk cytosol, in addition to the Cvt complex, to the vacuole. prAPI is transported via both vesicle types. A recombinant, cytosolic marker protein, Pho8Δ60p, is transported to the vacuole via autophagy. Delivery of Pho8Δ60p to the vacuole can be monitored through cleavage of the COOH-terminal propeptide. 2, Vesicle size: Cvt vesicles are ∼150 nm in diameter, whereas autophagosomes are 300–900 nm in diameter. 3, Conditions for induction: the Cvt pathway is active in vegetative growth conditions while autophagy is induced under starvation conditions.