| Autor: |
Erinjeri, Annmary Paul, Wang, Xunyan, Williams, Rhianna, Chiozzi, Riccardo Zenezini, Thalassinos, Konstantinos, Labbadia, Johnathan |
| Předmět: |
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| Zdroj: |
Nature Communications; 11/12/2024, Vol. 15 Issue 1, p1-15, 15p |
| Abstrakt: |
Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and mitochondria associated protein degradation, and that this is complemented by UBQL-1-dependent turnover of NPL-4.1. As a consequence, mitochondrial network dynamics are altered, leading to increased lifespan. Together, our data establish that HSF-1 mediates lifespan extension through mitochondrial network adaptations that occur in response to down-tuning of components associated with organellar protein degradation pathways. Increased activity of heat shock factor 1 (HSF1) promotes longevity; however, the mechanisms underlying this are unclear. Here, the authors show that in the nematode worm Caenorhabditis elegans, HSF1 overexpression increases lifespan through ubiquilin-1-dependent mitochondrial network remodelling. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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