Abstract Summary/Description
Autophagy is the process of degradation of the intracellular components within lysosomes in mammals or vacuoles in yeast. Autophagy is activated by cellular stress, nutrient deprivation, or pathogen invasion, and is vital for cell survival during prolonged starvation. Lipophagy, which specifically targets lipid droplets (LDs) for degradation, is conserved in various organisms and proceeds via direct interaction of LDs with vacuoles in yeast. Recent studies have shown that LDs are tagged with ubiquitin under lipophagy-inducing conditions. The E3 ubiquitin ligase, Rsp5, plays a crucial role by transferring ubiquitin to substrates and is involved in lipid biosynthesis, stress responses, and regulates several ubiquitin-dependent autophagic pathways. On the other hand, the ubiquitin-binding protein, Ubx5, has been shown to selectively degrade the dysfunctional Cdc48 by selective autophagy in yeast. We investigated the involvement of Rsp5 and Ubx5 in nitrogen starvation-induced lipophagy using mutant variants of these proteins. First, we found that Rsp5 is essential for lipophagy in yeast under nitrogen starvation conditions, as evidenced by the impairment of lipophagy in the rsp5-1 ts-mutant and RSP5 overexpression strains. We also found that the deletion of UBX5 gene in Saccharomyces cerevisiae impairs lipophagy under nitrogen starvation conditions. Therefore, we propose a model where Rsp5 ubiquitinates LDs and Ubx5 recognizes the ubiquitinated LDs for their autophagic degradation in the vacuole.
