Ubiquitin-binding autophagic receptors in yeast: Cue5 and beyond

The selectivity in selective macroautophagy/autophagy pathways is achieved via selective autophagy receptors (SARs) - proteins that bind a ligand on the substrate to be degraded and an Atg8-family protein on the growing autophagic membrane, phagophore, effectively bridging them. In mammals, the most common ligand of SARs is ubiquitin, a small protein modifier that tags substrates for their preferential degradation by autophagy. Consequently, most common SARs are ubiquitin-binding SARs, such as SQSTM1/p62 (sequestosome 1). Surprisingly, there is only one SAR of this type in yeast - Cue5, which acts as the receptor for aggrephagy and proteaphagy - pathways that remove ubiquitinated protein aggregates and proteasomes, respectively. However, recent studies described ubiquitin-dependent autophagic pathways that do not require Cue5, e.g. the stationary phase lipophagy for lipid droplets or nitrogen starvation-induced mitophagy for mitochondria. What is the role of ubiquitin in these pathways? Here, we propose that ubiquitinated lipid droplets and mitochondria are recognized by alternative ubiquitin-binding SARs. Our analysis identifies proteins that could potentially fulfill this role in yeast. We think that matching of ubiquitin-dependent (but Cue5-independent) autophagic pathways with ubiquitin- and Atg8-binding proteins enlisted here might uncover novel ubiquitin-binding SARs in yeast.

Automated summary

Selective autophagy pathways rely on selective autophagy receptors (SARs) to recognize and bridge the substrate to be degraded and the autophagic membrane. Ubiquitin is the common ligand for SARs in mammals, but yeast has only one SAR called Cue5. However, recent studies suggest that ubiquitin-dependent autophagic pathways in yeast may involve alternative ubiquitin-binding SARs. The identification of potential ubiquitin-binding proteins in yeast could lead to the discovery of novel SARs.