A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-09-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002284 |
| _version_ | 1797680694747463680 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Raimund Jung |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T23:33:46Z |
| format | Article |
| id | doaj.art-6e413ad3f27943b5974f39bac00f3cda |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-03-11T23:33:46Z |
| publishDate | 2023-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-6e413ad3f27943b5974f39bac00f3cda2023-09-20T05:31:04ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-09-01219e300228410.1371/journal.pbio.3002284A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.Raimund JungMarie C LechlerAna Fernandez-VillegasChyi Wei ChungHarry C JonesYoon Hee ChoiMaximilian A ThompsonChristian RödelspergerWaltraud RöselerGabriele S Kaminski SchierleRalf J SommerDella C DavidDuring 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.https://doi.org/10.1371/journal.pbio.3002284 |
| spellingShingle | 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 A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. PLoS Biology |
| title | A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. |
| title_full | A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. |
| title_fullStr | A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. |
| title_full_unstemmed | A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. |
| title_short | A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. |
| title_sort | safety mechanism enables tissue specific resistance to protein aggregation during aging in c elegans |
| url | https://doi.org/10.1371/journal.pbio.3002284 |
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