Cellular Strategies of Protein Quality Control
TLDR
The spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation are discussed.Abstract:
Eukaryotic cells must contend with a continuous stream of misfolded proteins that compromise the cellular protein homeostasis balance and jeopardize cell viability. An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome. Cellular protein quality control relies on three distinct yet interconnected strategies whereby misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially harmful misfolded species. Molecular chaperones play a critical role in determining the fate of misfolded proteins in the cell. Here, we discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation.read more
Citations
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Journal ArticleDOI
Protein misfolding in neurodegenerative diseases: implications and strategies
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TL;DR: Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways.
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Human Hsp70 Disaggregase Reverses Parkinson’s-Linked α-Synuclein Amyloid Fibrils
Xuechao Gao,Xuechao Gao,Marta Carroni,Carmen Nussbaum-Krammer,Carmen Nussbaum-Krammer,Axel Mogk,Axel Mogk,Nadinath B. Nillegoda,Nadinath B. Nillegoda,Anna Szlachcic,Anna Szlachcic,D. Lys Guilbride,Helen R. Saibil,Matthias P. Mayer,Bernd Bukau,Bernd Bukau +15 more
TL;DR: It is shown that a specific combination of human Hsc70 chaperone, the class B J-protein DNAJB1, and an Hsp110 family nucleotide exchange factor provide ATP-dependent activity that disassembles amyloids within minutes via combined fibril fragmentation and depolymerization.
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Spatial sequestration of misfolded proteins by a dynamic chaperone pathway enhances cellular fitness during stress
TL;DR: Q-body formation and clearance depends on an intact cortical ER and a complex chaperone network that is affected by rapamycin and impaired during chronological ageing and enhances cellular fitness during stress, and concludes that spatial sequestration of misfolded proteins in Q-bodies is an early quality control strategy occurring synchronously with degradation to clear the cytoplasm of potentially toxic species.
Journal ArticleDOI
Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition
Stephanie B.M. Miller,Chi-Ting Ho,Juliane Winkler,Maria Khokhrina,Annett Neuner,Mohamed Y H Mohamed,D. Lys Guilbride,Karsten Richter,Michael Lisby,Elmar Schiebel,Axel Mogk,Bernd Bukau +11 more
TL;DR: It is shown that JUNQ unexpectedly resides inside the nucleus, defining a new intranuclear quality control compartment, INQ, for the deposition of both nuclear and cytosolic misfolded proteins, irrespective of ubiquitination.
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