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.
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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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