Journal Article

DZNE-2023-00908

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.

Jung, R. (First author)DZNE* ; Lechler, M.DZNE* ; Fernandez-Villegas, A. ; Chung, C. W. ; Jones, H. C. ; Choi, Y. H. ; Thompson, M. A. ; Rödelsperger, C. ; Röseler, W. ; Kaminski Schierle, G. S. ; Sommer, R. J. ; David, D. (Last author)DZNE*

2023
PLoS Lawrence, KS

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Please use a persistent id in citations: doi:10.1371/journal.pbio.3002284

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.

Keyword(s): Animals (MeSH) ; Caenorhabditis elegans (MeSH) ; Protein Aggregates (MeSH) ; Aging (MeSH) ; Proteasome Endopeptidase Complex (MeSH) ; Proteostasis (MeSH) ; Protein Aggregates ; Proteasome Endopeptidase Complex

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Contributing Institute(s):

1. Protein Aggregation and Aging (AG David)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

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