Ubiquitylation by the Ltn1 E3 ligase protects 60S ribosomes from starvation-induced selective autophagy

J Cell Biol. 2014 Mar 17;204(6):909-17. doi: 10.1083/jcb.201308139. Epub 2014 Mar 10.


Autophagy, the process by which proteins or organelles are engulfed by autophagosomes and delivered for vacuolar/lysosomal degradation, is induced to ensure survival under starvation and other stresses. A selective autophagic pathway for 60S ribosomal subunits elicited by nitrogen starvation in yeast-ribophagy-was recently described and requires the Ubp3-Bre5 deubiquitylating enzyme. This discovery implied that an E3 ligases act upstream, whether inhibiting the process or providing an initial required signal. In this paper, we show that Ltn1/Rkr1, a 60S ribosome-associated E3 implicated in translational surveillance, acts as an inhibitor of 60S ribosomal subunit ribophagy and is antagonized by Ubp3. The ribosomal protein Rpl25 is a relevant target. Its ubiquitylation is Ltn1 dependent and Ubp3 reversed, and mutation of its ubiquitylation site rendered ribophagy less dependent on Ubp3. Consistently, the expression of Ltn1-but not Ubp3-rapidly decreased after starvation, presumably to allow ribophagy to proceed. Thus, Ltn1 and Ubp3-Bre5 likely contribute to adapt ribophagy activity to both nutrient supply and protein translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Enzyme Repression
  • Gene Expression
  • Gene Expression Regulation, Fungal
  • Gene Knockout Techniques
  • Nitrogen / metabolism
  • Ribosomal Proteins / metabolism*
  • Ribosome Subunits, Large, Eukaryotic / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Physiological
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination*


  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • ribosomal protein L25
  • Ltn1 protein, S cerevisiae
  • Ubiquitin-Protein Ligases
  • Endopeptidases
  • UBP3 protein, S cerevisiae
  • Nitrogen