NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in 
chemosensory C. elegans mutants

Guerrero, G. A.; Derisbourg, M. J.; Mayr, F. A. M.C.; Wester, L. E.; Giorda, M.; Dinort, J. E.; Hartman, M. D.; Schilling, K.; Alonso-De Gennaro, M. J.; Lu, R. J.; Benayoun, B. A.; Denzel, M.

doi:10.7554/eLife.53174

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NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants

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Guerrero, G. A.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Derisbourg, M. J.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Mayr, F. A. M.C.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278061

Wester, L. E.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278064

Dinort, J. E.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Hartman, M. D.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278068

Schilling, K.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons278071

Alonso-De Gennaro, M. J.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

/persons/resource/persons179771

Denzel, M.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/34448454
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Citation

Guerrero, G. A., Derisbourg, M. J., Mayr, F. A. M., Wester, L. E., Giorda, M., Dinort, J. E., et al. (2021). NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants. Elife, 10, e53174. doi:10.7554/eLife.53174.

Cite as: https://hdl.handle.net/21.11116/0000-000A-F9E0-0

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.