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

Sanzo-Machuca, A; Monje Moreno, JM; Casado-Navarro, R; Karakuzu, O; Guerrero-Gomez, D; Fierro-Gonzalez, JC; Swoboda, P; ... Miranda-Vizuete, A; + view all (2019) Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1. Redox Biology , 24 , Article 101178. 10.1016/j.redox.2019.101178. Green open access

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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 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.

Type: Article
Title: Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.redox.2019.101178
Publisher version: https://doi.org/10.1016/j.redox.2019.101178
Language: English
Additional information: © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Caenorhabditis elegans, Dauer, Food-leaving, Lips-6, Longevity, Male, Redox, Skn-1, Thioredoxin, EARLY EMBRYONIC LETHALITY, ESCHERICHIA-COLI, MITOCHONDRIAL THIOREDOXIN, DEOXYRIBONUCLEIC-ACID, REDUCTASE, CHAPERONE, TRX-1, SKN-1, REPLICATION, LONGEVITY
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10084271
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