Selective autophagy: ubiquitin-mediated recognition and beyond.
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.
Kraft
Claudine
C
Institute of Biochemistry, ETH Zürich, Schafmattstrasse 18, CH-8093 Zürich, Switzerland.
Peter
Matthias
M
Hofmann
Kay
K
D000375:Aging / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D005057:Eukaryotic Cells / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008954:Models, Biological; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
D002352:Carrier Proteins; D011506:Proteins; D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
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