Selective autophagy: ubiquitin-mediated recognition and beyond

Nat Cell Biol. 2010 Sep;12(9):836-41. doi: 10.1038/ncb0910-836.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Autophagy / physiology*
  • Carrier Proteins / metabolism
  • Eukaryotic Cells / physiology
  • Evolution, Molecular
  • Humans
  • Inclusion Bodies / metabolism
  • Models, Biological
  • Phylogeny
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Folding
  • Protein Interaction Domains and Motifs / physiology
  • Proteins / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitinated Proteins / metabolism
  • Ubiquitination / physiology*


  • Carrier Proteins
  • Proteins
  • Ubiquitin
  • Ubiquitinated Proteins
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex