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@ARTICLE{Jung:263974,
author = {Jung, Raimund and Lechler, Marie and Fernandez-Villegas,
Ana and Chung, Chyi Wei and Jones, Harry C and Choi, Yoon
Hee and Thompson, Maximilian A and Rödelsperger, Christian
and Röseler, Waltraud and Kaminski Schierle, Gabriele S and
Sommer, Ralf J and David, Della},
title = {{A} safety mechanism enables tissue-specific resistance to
protein aggregation during aging in {C}. elegans.},
journal = {PLoS biology},
volume = {21},
number = {9},
issn = {1544-9173},
address = {Lawrence, KS},
publisher = {PLoS},
reportid = {DZNE-2023-00908},
pages = {e3002284},
year = {2023},
abstract = {During 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.},
keywords = {Animals / Caenorhabditis elegans / Protein Aggregates /
Aging / Proteasome Endopeptidase Complex / Proteostasis /
Protein Aggregates (NLM Chemicals) / Proteasome
Endopeptidase Complex (NLM Chemicals)},
cin = {AG David},
ddc = {610},
cid = {I:(DE-2719)1210004},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC10501630},
pubmed = {pmid:37708127},
doi = {10.1371/journal.pbio.3002284},
url = {https://pub.dzne.de/record/263974},
}