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Selective autophagy: ubiquitin-mediated recognition and beyond

Nature Cell Biology volume 12, pages 836–841 (2010)Cite this article

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Abstract

Eukaryotic cells use autophagy and the ubiquitin–proteasome system as their major protein degradation pathways. Whereas the ubiquitin–proteasome system is involved in the rapid degradation of proteins, autophagy pathways can selectively remove protein aggregates and damaged or excess organelles. Proteasome-mediated degradation requires previous ubiquitylation of the cargo, which is then recognized by ubiquitin receptors directing it to 26S proteasomes. Although autophagy has long been viewed as a random cytoplasmic degradation system, the involvement of ubiquitin as a specificity factor for selective autophagy is rapidly emerging. Recent evidence also suggests active crosstalk between proteasome-mediated degradation and selective autophagy. Here, we discuss the molecular mechanisms that link autophagy and the proteasome system, as well as the emerging roles of ubiquitin and ubiquitin-binding proteins in selective autophagy. On the basis of the evolutionary history of autophagic ubiquitin receptors, we propose a common origin for metazoan ubiquitin-dependent autophagy and the cytoplasm-to-vacuole targeting pathway of yeast.

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Figure 1: Degradation routes for misfolded proteins.
Figure 2: Direct and indirect ubiquitin-binding proteins in autophagy.
Figure 3: Domain architecture of the p62/NBR1/Atg19 family.

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Acknowledgements

We thank Reinhard Dechant and Jason Mercer for critical reading of the manuscript. C.K. is supported by a Marie-Heim Vögtlin fellowship from the Swiss National Science Foundation (SNF). M.P. is a member of the Competence Center for Systems Physiology and Metabolic Diseases (SPMD), and supported by grants from the SNF, SystemsX.ch and the Eidgenössische Technische Hochschule Zürich. K.H. is supported by the Deutsche Forschungsgemeinschaft priority programme SPP1365.

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Authors and Affiliations

  1. Claudine Kraft and Matthias Peter are in the Institute of Biochemistry, ETH Zürich, Schafmattstrasse 18, CH-8093 Zürich, Switzerland. matthias.peter@bc.biol.ethz.ch,

    Claudine Kraft & Matthias Peter

  2. Kay Hoffman is in the Miltenyi Biotec GmbH, Friedrich-Ebert-Strasse 68, 51429 Bergisch-Gladbach, Germany. kay.hofmann@miltenyibiotec.de,

    Kay Hofmann

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Kraft, C., Peter, M. & Hofmann, K. Selective autophagy: ubiquitin-mediated recognition and beyond. Nat Cell Biol 12, 836–841 (2010). https://doi.org/10.1038/ncb0910-836

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