A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.

Autor: Raimund Jung, Marie C Lechler, Ana Fernandez-Villegas, Chyi Wei Chung, Harry C Jones, Yoon Hee Choi, Maximilian A Thompson, Christian Rödelsperger, Waltraud Röseler, Gabriele S Kaminski Schierle, Ralf J Sommer, Della C David
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: PLoS Biology, Vol 21, Iss 9, p e3002284 (2023)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.3002284
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje