| Autor: |
Ángela Sanzo-Machuca, José Manuel Monje Moreno, Rafael Casado-Navarro, Ozgur Karakuzu, David Guerrero-Gómez, Juan Carlos Fierro-González, Peter Swoboda, Manuel J. Muñoz, Danielle A. Garsin, José Rafael Pedrajas, Arantza Barrios, Antonio Miranda-Vizuete |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 24, Iss , Pp - (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2019.101178 |
| Popis: |
Thioredoxins (TRX) are traditionally considered as enzymes catalyzing redox reactions. However, redox-independent functions of thioredoxins have been described in different organisms, although the underlying molecular mechanisms are yet unknown. We report here the characterization of the first generated endogenous redox-inactive thioredoxin in an animal model, the TRX-1 in the nematode Caenorhabditis elegans. We find that TRX-1 dually regulates the formation of an endurance larval stage (dauer) by interacting with the insulin pathway in a redox-independent manner and the cGMP pathway in a redox-dependent manner. Moreover, the requirement of TRX-1 for the extended longevity of worms with compromised insulin signalling or under calorie restriction relies on TRX-1 redox activity. In contrast, the nuclear translocation of the SKN-1 transcription factor and increased LIPS-6 protein levels in the intestine upon trx-1 deficiency are strictly redox-independent. Finally, we identify a novel function of C. elegans TRX-1 in male food-leaving behaviour that is redox-dependent. Taken together, our results position C. elegans as an ideal model to gain mechanistic insight into the redox-independent functions of metazoan thioredoxins, overcoming the limitations imposed by the embryonic lethal phenotypes of thioredoxin mutants in higher organisms. Keywords: Caenorhabditis elegans, Dauer, Food-leaving, Lips-6, Longevity, Male, Redox, Skn-1, Thioredoxin |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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