Mature Ribosomes Are Selectively Degraded Upon Starvation by an Autophagy Pathway Requiring the Ubp3p/Bre5p Ubiquitin Protease

Nat Cell Biol. 2008 May;10(5):602-10. doi: 10.1038/ncb1723. Epub 2008 Apr 6.

Abstract

Eukaryotic cells use autophagy and the ubiquitin-proteasome system (UPS) as their major protein degradation pathways. Whereas the UPS is required for the rapid degradation of proteins when fast adaptation is needed, autophagy pathways selectively remove protein aggregates and damaged or excess organelles. However, little is known about the targets and mechanisms that provide specificity to this process. Here we show that mature ribosomes are rapidly degraded by autophagy upon nutrient starvation in Saccharomyces cerevisiae. Surprisingly, this degradation not only occurs by a non-selective mechanism, but also involves a novel type of selective autophagy, which we term 'ribophagy'. A genetic screen revealed that selective degradation of ribosomes requires catalytic activity of the Ubp3p/Bre5p ubiquitin protease. Although ubp3Delta and bre5Delta cells strongly accumulate 60S ribosomal particles upon starvation, they are proficient in starvation sensing and in general trafficking and autophagy pathways. Moreover, ubiquitination of several ribosomal subunits and/or ribosome-associated proteins was specifically enriched in ubp3Delta cells, suggesting that the regulation of ribophagy by ubiquitination may be direct. Interestingly, ubp3Delta cells are sensitive to rapamycin and nutrient starvation, implying that selective degradation of ribosomes is functionally important in vivo. Taken together, our results suggest a link between ubiquitination and the regulated degradation of mature ribosomes by autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Animals
  • Autophagy / physiology*
  • Autophagy-Related Protein 8 Family
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nitrogen / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / physiology*
  • Starvation*
  • Ubiquitin / metabolism

Substances

  • ATG8 protein, S cerevisiae
  • Autophagy-Related Protein 8 Family
  • Carrier Proteins
  • Microtubule-Associated Proteins
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitin
  • Endopeptidases
  • Aminopeptidases
  • APE1 protein, S cerevisiae
  • Bre5 protein, S cerevisiae
  • UBP3 protein, S cerevisiae
  • Nitrogen