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Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease

Nature Cell Biology volume 10, pages 602–610 (2008)Cite this article

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 organelles1. 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 ubp3Δ and bre5Δ 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 ubp3Δ cells, suggesting that the regulation of ribophagy by ubiquitination may be direct. Interestingly, ubp3Δ 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.

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Figure 1: Nitrogen starvation induces ribosome degradation by means of a selective autophagy pathway.
Figure 2: Ribophagy requires active ubiquitin protease Ubp3p and its regulatory subunit Bre5p.
Figure 3: General autophagy is not affected in ubp3Δ and bre5Δ cells.
Figure 4: Cells lacking Ubp3p/Bre5p activity are defective in selective 60S turnover and show increased ubiquitination of ribosomes or associated proteins.
Figure 5: Our data suggest that ubiquitination of ribosomal subunits or associated proteins may protect mature ribosomes from degradation by a selective autophagy pathway.

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Acknowledgements

We thank Jean-Marc Galan, Ed Hurt, Vikram Panse, Sabine Rospert, Matthias Seedorf and Gwénael Rabut for plasmids and antibodies; Christine Rupp for technical assistance; and Sebastian Leidel and Reinhard Dechant for critical reading of the manuscript. A. D. is part of the Center for Systems Physiology and Metabolic Diseases (SPMD) and the Molecular Life Science PhD programme of the UNI and ETH Zürich. This work was supported by an EMBO long-term fellowship (C.K.), and grants from the Swiss National Science Foundation and the Eidgenössische Technische Hochschule, Zürich (M.P.).

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  1. Institute of Biochemistry, HPM, ETH Hönggerberg, Zürich, 8093, Switzerland

    Claudine Kraft, Anna Deplazes, Marc Sohrmann & Matthias Peter

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Correspondence to Claudine Kraft or Matthias Peter.

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Supplementary Figures S1, S2, S3, S4, S5, S6 and Supplementary Tables 1, 2, 3 (PDF 6112 kb)

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Kraft, C., Deplazes, A., Sohrmann, M. et al. Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat Cell Biol 10, 602–610 (2008). https://doi.org/10.1038/ncb1723

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