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Lookup NU author(s): Emma Button, Emilia Dwyer, Elise McDonald, Dr Fiona Pearson, Dr Elizabeth VealORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Reactive oxygen species (ROS)-induced cell damage contributes to many diseases.However, ROS also contribute to cell signaling and immune defences. As ubiquitousthiol peroxidases, peroxiredoxins (Prdx) play integral roles in balancing ROS functions.High levels of Prdx6 are associated with increased metastasis and resistance tochemotherapy, rendering Prdx6 a therapeutic target for treatment of a broad range ofcancers. However, Prdx6 has additional activities, in lipid signalling and selenocysteinemetabolism, and it remains unclear how Prdx6’s thiol peroxidase activity contributes todisease. Here we have investigated the role/s of Prdx6 in the nematode wormCaenorhabditis elegans. Consistent with a ROS-protective role for PRDX-6, prdx-6mutant C. elegans exhibit elevated levels of lipid oxidation, more apoptotic corpses intheir germline and are more susceptible to the toxicity of diethyl maleate. However,unexpectedly, prdx-6 mutant C. elegans are more resistant to other forms of oxidativestress, long-lived and resistant to infection with two opportunistic human pathogens;the gram-positive bacteria Staphylococcus aureus and the dimorphic yeast Candidaalbicans. Our data suggest these phenotypes are associated with increased activity ofthe NHR-49(PPARα/HNF4) transcriptional regulator and intestinal expression of theFlavin monooxygenase, FMO-2. FMO-2 has a conserved, pro-survival function and isup-regulated in response to various stresses, including peroxides and S. aureusinfection. Here we reveal that fmo-2 expression is also increased as an NHR-49-dependent protective response to C. albicans. Consistent with increased NHR-49activity, prdx-6 mutant animals also contain increased levels of mono-unsaturated fattyacids. Accordingly, we propose that elevated expression of fmo-2 and other NHR-49up-regulated genes contribute to the increased arsenite resistance and innateimmunity of prdx-6 mutant animals. These findings further illustrate the complex rolesthat ROS, PRDX and lipid oxidation can play in oxidative stress resistance, immunityand ageing.
Author(s): Button EL, Dwyer E, Lewis JB, Mortensen MS, McDonald E, Butler E, Pearson F, Tang AE, Watts J, Veal EA
Publication type: Article
Publication status: Published
Journal: Redox Biology
Year: 2025
Pages: Epub ahead of print
Online publication date: 29/12/2025
Acceptance date: 22/12/2025
Date deposited: 26/12/2025
ISSN (electronic): 2213-2317
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.redox.2025.103992
DOI: 10.1016/j.redox.2025.103992
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