Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
Monje Moreno, José Manuel
Guerrero Gómez, David
Fierro-González, Juan Carlos
Muñoz, Manuel J.
Miranda Vizuete, Antonio
|Department||Instituto de Biomedicina de Sevilla (IBIS)|
|Published in||Redox Biology, 24, 101178-1-101178-8.|
|Abstract||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 ...
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.
|Cite||Sanzo-Machuca, Á., Monje Moreno, J.M., Casado-Navarro, R., Karakuzu, O., Guerrero Gómez, D., Fierro-González, J.C.,...,Miranda Vizuete, A. (2019). Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1. Redox Biology, 24, 101178-1-101178-8.|