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

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 gener...

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Autores: Sanzo-Machuca, Ángela, Monje Moreno, José Manuel, Casado-Navarro, Rafael, Karakuzu, Ozgur, Guerrero Gómez, David, Fierro-González, Juan Carlos, Swoboda, Peter, Muñoz, Manuel J., Miranda Vizuete, Antonio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/88465
Acceso en línea:https://hdl.handle.net/11441/88465
https://doi.org/10.1016/j.redox.2019.101178
Access Level:acceso abierto
Palabra clave:Caenorhabditis elegans
Dauer
Food-leaving
Lips-6
Longevity
Male
Redox
Skn-1
Thioredoxin
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spelling Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1Sanzo-Machuca, ÁngelaMonje Moreno, José ManuelCasado-Navarro, RafaelKarakuzu, OzgurGuerrero Gómez, DavidFierro-González, Juan CarlosSwoboda, PeterMuñoz, Manuel J.Miranda Vizuete, AntonioCaenorhabditis elegansDauerFood-leavingLips-6LongevityMaleRedoxSkn-1ThioredoxinThioredoxins (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.NIH Office of Research Infrastructure P40 OD010440Spanish Ministry of Economy and Competitiveness BFU2015- 64408-PFondo Social Europeo BFU2015- 64408-PNational Institute of Allergy and Infectious Diseases of the National Institutes of Health R01AI076406Elsevier2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/88465https://doi.org/10.1016/j.redox.2019.101178reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésRedox Biology, 24, 101178-1-101178-8.P40 OD010440R01AI076406BFU2015- 64408-Phttp://doi.org/10.1016/j.redox.2019.101178info:eu-repo/semantics/openAccessoai:idus.us.es:11441/884652026-06-17T12:51:07Z
dc.title.none.fl_str_mv Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
title Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
spellingShingle Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
Sanzo-Machuca, Ángela
Caenorhabditis elegans
Dauer
Food-leaving
Lips-6
Longevity
Male
Redox
Skn-1
Thioredoxin
title_short Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
title_full Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
title_fullStr Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
title_full_unstemmed Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
title_sort Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
dc.creator.none.fl_str_mv Sanzo-Machuca, Ángela
Monje Moreno, José Manuel
Casado-Navarro, Rafael
Karakuzu, Ozgur
Guerrero Gómez, David
Fierro-González, Juan Carlos
Swoboda, Peter
Muñoz, Manuel J.
Miranda Vizuete, Antonio
author Sanzo-Machuca, Ángela
author_facet Sanzo-Machuca, Ángela
Monje Moreno, José Manuel
Casado-Navarro, Rafael
Karakuzu, Ozgur
Guerrero Gómez, David
Fierro-González, Juan Carlos
Swoboda, Peter
Muñoz, Manuel J.
Miranda Vizuete, Antonio
author_role author
author2 Monje Moreno, José Manuel
Casado-Navarro, Rafael
Karakuzu, Ozgur
Guerrero Gómez, David
Fierro-González, Juan Carlos
Swoboda, Peter
Muñoz, Manuel J.
Miranda Vizuete, Antonio
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Caenorhabditis elegans
Dauer
Food-leaving
Lips-6
Longevity
Male
Redox
Skn-1
Thioredoxin
topic Caenorhabditis elegans
Dauer
Food-leaving
Lips-6
Longevity
Male
Redox
Skn-1
Thioredoxin
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/88465
https://doi.org/10.1016/j.redox.2019.101178
url https://hdl.handle.net/11441/88465
https://doi.org/10.1016/j.redox.2019.101178
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Redox Biology, 24, 101178-1-101178-8.
P40 OD010440
R01AI076406
BFU2015- 64408-P
http://doi.org/10.1016/j.redox.2019.101178
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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