RT Journal Article
T1 Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1.
A1 Sanzo-Machuca, Ángela
A1 Monje Moreno, José Manuel
A1 Casado-Navarro, Rafael
A1 Karakuzu, Ozgur
A1 Guerrero-Gómez, David
A1 Fierro-González, Juan Carlos
A1 Swoboda, Peter
A1 Muñoz, Manuel J
A1 Garsin, Danielle A
A1 Pedrajas, José Rafael
A1 Barrios, Arantza
A1 Miranda-Vizuete, Antonio
K1 Caenorhabditis elegans
K1 Dauer
K1 Food-leaving
K1 Lips-6
K1 Longevity
K1 Male
K1 Redox
K1 Skn-1
K1 Thioredoxin
AB 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.
YR 2019
FD 2019-03-27
LK http://hdl.handle.net/10668/13795
UL http://hdl.handle.net/10668/13795
LA en
DS RISalud
RD Apr 5, 2025