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Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1

AuthorsSanzo-Machuca, Ángela; Monje Moreno, José Manuel; Casado-Navarro, Rafael; Karakuzu, Ozgur; Guerrero-Gómez, David; Fierro-González, Juan Carlos; Swoboda, Peter; Pedrajas, José R.; Barrios, Arantxa; Miranda-Vizuete, Antonio
KeywordsCaenorhabditis elegans
Issue DateJun-2019
CitationRedox Biology 24: 101178 (2019)
AbstractThioredoxins (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.
Publisher version (URL)http://dx.doi.org/10.1016/j.redox.2019.101178
Identifiersdoi: 10.1016/j.redox.2019.101178
issn: 2213-2317
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