Universität zu Köln

Guerrero, Gabriel A., Derisbourg, Maxime J., Mayr, Felix A. M. C., Wester, Laura E., Giorda, Marco, Dinort, J. Eike, Hartman, Matias D., Schilling, Klara, Alonso-De Gennaro, Maria Jose, Lu, Ryan J., Benayoun, Berenice A. and Denzel, Martin S. (2021). NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants. eLife, 10. CAMBRIDGE: eLIFE SCIENCES PUBL LTD. ISSN 2050-084X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Guerrero, Gabriel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Derisbourg, Maxime J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mayr, Felix A. M. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wester, Laura E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Giorda, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinort, J. Eike UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartman, Matias D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schilling, Klara UNSPECIFIED UNSPECIFIED UNSPECIFIED Alonso-De Gennaro, Maria Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Lu, Ryan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benayoun, Berenice A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Denzel, Martin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-578845
DOI:	10.7554/eLife.53174; 10.7554/eLife.53174.sa1; 10.7554/eLife.53174.sa2
Journal or Publication Title:	eLife
Volume:	10
Date:	2021
Publisher:	eLIFE SCIENCES PUBL LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UNFOLDED PROTEIN RESPONSE; CAENORHABDITIS-ELEGANS; LIFE-SPAN; HEXOSAMINE PATHWAY; GENES; TUNICAMYCIN; IVERMECTIN; PARAQUAT; GENETICS; XBP-1 Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57884