Cellular quality control by the ubiquitin-proteasome system and autophagy

To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt to new environmental conditions and to prevent prolonged damage. We discuss the importance of two major quality control systems responsible for degradation of proteins and organelles in eukaryotic ce...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2019-11, Vol.366 (6467), p.818-822
Main Authors: Pohl, Christian, Dikic, Ivan
Format: Article
Language:English
Subjects:
Animals
Autophagy
Humans
Macroautophagy
Organelles - metabolism
Proteasome Endopeptidase Complex - physiology
Proteolysis
Ubiquitin - physiology
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Summary:To achieve homeostasis, cells evolved dynamic and self-regulating quality control processes to adapt to new environmental conditions and to prevent prolonged damage. We discuss the importance of two major quality control systems responsible for degradation of proteins and organelles in eukaryotic cells: the ubiquitin-proteasome system (UPS) and autophagy. The UPS and autophagy form an interconnected quality control network where decision-making is self-organized on the basis of biophysical parameters (binding affinities, local concentrations, and avidity) and compartmentalization (through membranes, liquid-liquid phase separation, or the formation of aggregates). We highlight cellular quality control factors that delineate their differential deployment toward macromolecular complexes, liquid-liquid phase-separated subcellular structures, or membrane-bound organelles. Finally, we emphasize the need for continuous promotion of quantitative and mechanistic research into the roles of the UPS and autophagy in human pathophysiology.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aax3769