Ubiquitin orchestrates proteasome dynamics between proliferation and quiescence in yeast

Mol Biol Cell. 2017 Sep 15;28(19):2479-2491. doi: 10.1091/mbc.E17-03-0162. Epub 2017 Aug 2.

Abstract

Proteasomes are essential for protein degradation in proliferating cells. Little is known about proteasome functions in quiescent cells. In nondividing yeast, a eukaryotic model of quiescence, proteasomes are depleted from the nucleus and accumulate in motile cytosolic granules termed proteasome storage granules (PSGs). PSGs enhance resistance to genotoxic stress and confer fitness during aging. Upon exit from quiescence PSGs dissolve, and proteasomes are rapidly delivered into the nucleus. To identify key players in PSG organization, we performed high-throughput imaging of green fluorescent protein (GFP)-labeled proteasomes in the yeast null-mutant collection. Mutants with reduced levels of ubiquitin are impaired in PSG formation. Colocalization studies of PSGs with proteins of the yeast GFP collection, mass spectrometry, and direct stochastic optical reconstitution microscopy of cross-linked PSGs revealed that PSGs are densely packed with proteasomes and contain ubiquitin but no polyubiquitin chains. Our results provide insight into proteasome dynamics between proliferating and quiescent yeast in response to cellular requirements for ubiquitin-dependent degradation.

MeSH terms

  • Cell Nucleus / metabolism
  • Cell Proliferation / physiology
  • Cytoplasm / metabolism
  • Cytoplasmic Granules / metabolism
  • Cytosol / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Ubiquitin / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex