| Autor: |
Jung, Raimund, Lechler, Marie C., Fernandez-Villegas, Ana, Chung, Chyi Wei, Jones, Harry C., Choi, Yoon Hee, Thompson, Maximilian A., Rödelsperger, Christian, Röseler, Waltraud, Kaminski Schierle, Gabriele S., Sommer, Ralf J., David, Della C. |
| Předmět: |
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| Zdroj: |
PLoS Biology; 9/14/2023, Vol. 21 Issue 9, p1-25, 25p, 4 Graphs |
| Abstrakt: |
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. This study shows that during failure of core protein quality control in C. elegans, a specialized anti-aggregation mechanism relying on intracellular pathogen response factors and lysosomal mediated degradation is triggered, promoting tissue-specific resilience to age-dependent protein aggregation and its proteotoxicity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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