title: Autophagic Turnover of Inactive 26S Proteasomes in Yeast Is Directed by the Ubiquitin Receptor Cue5 and the Hsp42 Chaperone.
abstract: The autophagic clearance of 26S proteasomes (proteaphagy) is an important homeostatic mechanism within the ubiquitin system that modulates proteolytic capacity and eliminates damaged particles. Here, we define two proteaphagy routes in yeast that respond to either nitrogen starvation or particle inactivation. Whereas the core autophagic machineries required for Atg8 lipidation and vesiculation are essential for both routes, the upstream Atg1 kinase participates only in starvation-induced proteaphagy. Following inactivation, 26S proteasomes become extensively modified with ubiquitin. Although prior studies with Arabidopsis implicated RPN10 in tethering ubiquitylated proteasomes to ATG8 lining the autophagic membranes, yeast proteaphagy employs the evolutionarily distinct receptor Cue5, which simultaneously binds ubiquitin and Atg8. Proteaphagy of inactivated proteasomes also requires the oligomeric Hsp42 chaperone, suggesting that ubiquitylated proteasomes are directed by Hsp42 to insoluble protein deposit (IPOD)-type structures before encapsulation. Together, Cue5 and Hsp42 provide a quality control checkpoint in yeast directed at recycling dysfunctional 26S proteasomes.
authors.affiliation: Department of Genetics, University of Wisconsin, 425 Henry Mall, Madison, WI 53706, USA; Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Marshall
authors.affiliation: Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA.
authors.forename: Fionn
authors.initials: F
authors.lastname: McLoughlin
authors.affiliation: Department of Genetics, University of Wisconsin, 425 Henry Mall, Madison, WI 53706, USA; Department of Biology, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, USA. Electronic address: rdvierstra@wustl.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Vierstra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017360:Arabidopsis / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000594940:Cue5 protein, S cerevisiae; C098005:HSP42 protein, S cerevisiae; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease
keywords: 26S proteasome; autophagy; insoluble protein deposit (IPOD); nitrogen starvation; proteaphagy; protein chaperone; ubiquitin; yeast