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000263974 1001_ $$0P:(DE-2719)2811479$$aJung, Raimund$$b0$$eFirst author
000263974 245__ $$aA safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.
000263974 260__ $$aLawrence, KS$$bPLoS$$c2023
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000263974 520__ $$aDuring aging, proteostasis capacity declines and distinct proteins become unstable and can accumulate as protein aggregates inside and outside of cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of cytoplasmic protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of 3 core protein quality control systems, namely chaperones, the proteasome, and macroautophagy, leads to lower levels of age-dependent protein aggregation in Caenorhabditis elegans pharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism that selectively targets newly synthesized proteins to suppress their aggregation and associated proteotoxicity. The safety mechanism relies on macroautophagy-independent lysosomal degradation and involves several previously uncharacterized components of the intracellular pathogen response (IPR). We propose that this protective mechanism engages an anti-aggregation machinery targeting aggregating proteins for lysosomal degradation.
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000263974 650_2 $$2MeSH$$aAnimals
000263974 650_2 $$2MeSH$$aCaenorhabditis elegans
000263974 650_2 $$2MeSH$$aProtein Aggregates
000263974 650_2 $$2MeSH$$aAging
000263974 650_2 $$2MeSH$$aProteasome Endopeptidase Complex
000263974 650_2 $$2MeSH$$aProteostasis
000263974 650_7 $$2NLM Chemicals$$aProtein Aggregates
000263974 650_7 $$0EC 3.4.25.1$$2NLM Chemicals$$aProteasome Endopeptidase Complex
000263974 7001_ $$0P:(DE-2719)2810617$$aLechler, Marie$$b1
000263974 7001_ $$aFernandez-Villegas, Ana$$b2
000263974 7001_ $$aChung, Chyi Wei$$b3
000263974 7001_ $$aJones, Harry C$$b4
000263974 7001_ $$aChoi, Yoon Hee$$b5
000263974 7001_ $$aThompson, Maximilian A$$b6
000263974 7001_ $$aRödelsperger, Christian$$b7
000263974 7001_ $$aRöseler, Waltraud$$b8
000263974 7001_ $$aKaminski Schierle, Gabriele S$$b9
000263974 7001_ $$aSommer, Ralf J$$b10
000263974 7001_ $$0P:(DE-2719)2810353$$aDavid, Della$$b11$$eLast author
000263974 773__ $$0PERI:(DE-600)2126773-X$$a10.1371/journal.pbio.3002284$$gVol. 21, no. 9, p. e3002284 -$$n9$$pe3002284$$tPLoS biology$$v21$$x1544-9173$$y2023
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