CYTOPLASM-TO-VACUOLE TARGETING AND AUTOPHAGY EMPLOY THE SAME MACHINERY TO DELIVER PROTEINS TO THE YEAST VACUOLE

The vacuolar protein aminopeptidase I (API) uses a novel cytoplasm-to- vacuole targeting (Cvt) pathway. Complementation analysis of yeast mut ants defective for cytoplasm-to-vacuole protein targeting (cvt) and au tophagy (apg) revealed seven overlapping complementation groups betwee n these two sets of mutants. In addition, all 14 apg complementation g roups are defective in the delivery of API to the vacuole. Similarly, the majority of nonoverlapping cvt complementation groups appear to he at least partially defective in autophagy. Kinetic analyses of protei n delivery rates indicate that autophagic protein uptake is induced by nitrogen starvation, whereas Cvt is a constitutive biosynthetic pathw ay. However, the machinery governing Cvt is affected by nitrogen starv ation as targeting defects resulting from API overexpression can be re scued by induction of autophagy.