RT Journal Article
T1 Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
A1 Sanzo-Machuca, Ángela
A1 Monje, José Manuel
A1 Casado-Navarro, Rafael
A1 Karakuzu, Ozgur
A1 Guerrero-Gómez, David
A1 Fierro-González, Juan Carlos
A1 Swoboda, Peter
A1 Muñoz Ruiz, Manuel Jesús
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.
PB EUrope PMC
YR 2019
FD 2019-03-27
LK https://hdl.handle.net/10433/23796
UL https://hdl.handle.net/10433/23796
LA en
NO Redox Biology, 27 Mar 2019, 24:101178
NO AMV was supported by a grant from the Spanish Ministry of Economy and Competitiveness (BFU2015-64408-P), cofinanced by the Fondo Social Europeo (FEDER). DAG was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R01AI076406. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. AMV is a member of the GENIE and EU-ROS Cost Actions of the European Union.
NO Universidad Pablo de Olavide, Departamento de Biología Molecular e Ingeniería Bioquímica
NO Redox Homeostasis Group, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla
NO Department of Cell and Developmental Biology, University College London
NO Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston
NO Department of Biosciences and Nutrition, Karolinska Institute
NO Grupo de Bioquímica y Señalización Celular, Departamento de Biología Experimental, Universidad de Jaén
DS RIO
RD May 5, 2026