Cellular quality control by the ubiquitin-proteasome system and autophagy
By Christian Pohl, Ivan Dikic. Science, 2019
1,054 citations recorded by the source corpus.
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.
Subfields: Cell Biology, Epidemiology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/69db0001f30dcc21c10fc1ac2778405ddf4add69
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Citations in the corpus
- Targeted protein degradation: mechanisms, strategies and application (2022, background): “In general, proteasomes eliminate short-lived proteins and soluble misfolded proteins by the ubiquitin–proteasome system (UPS).(6,7) In contrast, lysosomes are responsible for degradation of long-lived proteins, insoluble protein aggregates, even entire organelles, macromolecular compounds, and intr”
- Hallmarks of neurodegenerative diseases. (2023, neutral): “130,156 Genes associated with PD exert crucial roles in autophagy, lysosomal function, and endolysoso-mal trafficking, 19,112,113,157 including several key proteins (i.e., LRRK2 , SYNJ1 , DNAJC6 , and DNAJC13 [RME - 8]) important for controlling endocytosis and autophagy at the synapse.”