TY  - JOUR
AU  - Jung, Raimund
AU  - Lechler, Marie
AU  - Fernandez-Villegas, Ana
AU  - Chung, Chyi Wei
AU  - Jones, Harry C
AU  - Choi, Yoon Hee
AU  - Thompson, Maximilian A
AU  - Rödelsperger, Christian
AU  - Röseler, Waltraud
AU  - Kaminski Schierle, Gabriele S
AU  - Sommer, Ralf J
AU  - David, Della
TI  - A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.
JO  - PLoS biology
VL  - 21
IS  - 9
SN  - 1544-9173
CY  - Lawrence, KS
PB  - PLoS
M1  - DZNE-2023-00908
SP  - e3002284
PY  - 2023
AB  - 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.
KW  - Animals
KW  - Caenorhabditis elegans
KW  - Protein Aggregates
KW  - Aging
KW  - Proteasome Endopeptidase Complex
KW  - Proteostasis
KW  - Protein Aggregates (NLM Chemicals)
KW  - Proteasome Endopeptidase Complex (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10501630
C6  - pmid:37708127
DO  - DOI:10.1371/journal.pbio.3002284
UR  - https://pub.dzne.de/record/263974
ER  -