The ubiquitin-proteasome system degrades fatty acid synthase under nitrogen starvation when autophagy is dysfunctional in Saccharomyces cerevisiae

Autophagy and the ubiquitin-proteasome system (UPS) are two major protein quality control mechanisms maintaining cellular proteostasis. In Saccharomyces cerevisiae, the de novo synthesis of saturated fatty acids is performed by a multienzyme complex known as fatty acid synthase (FAS). A recent study reported that yeast FAS is preferentially degraded by autophagy under nitrogen starvation. In this study, we examined the fate of FAS during nitrogen starvation when autophagy is dysfunctional. We found that the UPS compensates for FAS degradation in the absence of autophagy. Additionally, we discovered that the UPS-dependent degradation of Fas2 requires the E3 ubiquitin ligase Ubr1. Our findings highlight the complementary relationship between autophagy and the UPS. •The FAS complex is still degraded under nitrogen starvation in autophagy-deficient cells.•FAS is degraded by the UPS under autophagy-deficient starvation.•Ubr1 is necessary for efficient degradation of Fas2 under autophagy-deficient starvation.•Our findings highlight the complementary relationship between autophagy and the UPS.