NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
- Max Planck Institute for Biology of Ageing, Germany
- University of Southern California, United States
Abstract
Longevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory defective Caenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene osm-3 were significantly protected from tunicamycin-induced ER stress. While osm-3 lifespan extension is dependent on the key longevity factor DAF-16/FOXO, tunicamycin resistance was not. osm-3 mutants are protected from bacterial pathogens, which is pmk-1 p38 MAP kinase dependent while TM resistance was pmk-1 independent. Expression of P-glycoprotein (PGP) xenobiotic detoxification genes was elevated in osm-3 mutants and their knockdown or inhibition with verapamil suppressed tunicamycin resistance. The nuclear hormone receptor nhr-8 was necessary to regulate a subset of PGPs. We thus identify a cell-nonautonomous regulation of xenobiotic detoxification and show that separate pathways are engaged to mediate longevity, pathogen resistance, and xenobiotic detoxification in osm-3 mutants.
Data availability
Raw sequencing data were deposited to the NCBI Gene Expression Omnibus (GEO) under the accession number GSE144675.
Article and author information
Author details
Bérénice A Benayoun
Martin Sebastian Denzel
Funding
H2020 European Research Council (ERC-StG 640254)
- Martin Sebastian Denzel
Max-Planck-Gesellschaft
- Gabriel A Guerrero
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Elçin Ünal, University of California, Berkeley, United States
Publication history
- Preprint posted: October 30, 2019 (view preprint)
- Received: October 30, 2019
- Accepted: August 25, 2021
- Accepted Manuscript published: August 27, 2021 (version 1)
- Version of Record published: September 23, 2021 (version 2)
Copyright
© 2021, Guerrero et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
eLife 10:e53174.
https://doi.org/10.7554/eLife.53174
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