Eat or be eaten: The autophagic plight of inactive 26S proteasomes.

Two principal pathways in eukaryotes, namely the ubiquitin-proteasome system (UPS) and autophagy, mediate selective protein degradation. The UPS typically removes short-lived individual misfolded or regulatory polypeptides that have been tagged with polyubiquitin chains, whereas autophagy eliminates bulkier structures such as large protein complexes, insoluble protein aggregates, organelles, and invading intracellular pathogens. Protein degradation within the UPS is executed by the 26S proteasome, a large multisubunit proteolytic machine whose levels are tightly regulated transcriptionally and during assembly. Our recent studies identified a new mechanism for controlling 26S proteasome abundance through selective autophagy, which we term proteaphagy. This process is separately stimulated by nutrient starvation and proteasome inactivation, the latter occurring independently of ATG1 kinase regulation. Removal of inactive complexes is instead mediated by the proteasomal ubiquitin receptor RPN10, which can simultaneously bind both ubiquitinated proteasomes and lipidated ATG8 lining autophagic membranes.