Sanzo-Machuca, ÁngelaMonje Moreno, José ManuelCasado-Navarro, RafaelKarakuzu, OzgurGuerrero-Gómez, DavidFierro-González, Juan CarlosSwoboda, PeterMuñoz, Manuel JGarsin, Danielle APedrajas, José RafaelBarrios, ArantzaMiranda-Vizuete, Antonio2023-01-252023-01-252019-03-27http://hdl.handle.net/10668/13795Thioredoxins (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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Caenorhabditis elegansDauerFood-leavingLips-6LongevityMaleRedoxSkn-1ThioredoxinAmino Acid SubstitutionAnimalsBiomarkersCaenorhabditis elegansCaenorhabditis elegans ProteinsCysteineDNA Mutational AnalysisDNA-Binding ProteinsGene ExpressionMaleMutationOxidation-ReductionProtein TransportThioredoxinsTranscription Factorsresearch article30953965open access10.1016/j.redox.2019.1011782213-2317PMC6449771https://doi.org/10.1016/j.redox.2019.101178https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449771/pdf