Nuclear Hormone Receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans
- University of British Columbia, Canada
- University of Washington, United States
- University of Pittsburgh School of Medicine, United States
Abstract
Caenorhabditis elegans Nuclear Hormone Receptor NHR-49, an orthologue of mammalian Peroxisome Proliferator-Activated Receptor alpha (PPARα). We show that nhr-49 is required for animal survival in hypoxia and is synthetic lethal with hif-1 in this context, demonstrating that these factors act in parallel. RNA-seq analysis shows that in hypoxia nhr-49 regulates a set of genes that are hif-1-independent, including autophagy genes that promote hypoxia survival. We further show that Nuclear Hormone Receptor nhr-67 is a negative regulator and Homeodomain-interacting Protein Kinase hpk-1 is a positive regulator of the NHR-49 pathway. Together, our experiments define a new, essential hypoxia response pathway that acts in parallel with the well-known HIF-mediated hypoxia response.
Data availability
RNA-seq data have been deposited at NCBI Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) under the record GSE166788.All data generated or analysed during this study are included in the manuscript and Supplementary Tables. Raw data points from each N are shown in figures where-ever possible. See transparent reporting form for details.
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NHR-49 controls a HIF-1 independent hypoxia adaptation pathway in Caenorhabditis elegansNCBI Gene Expression Omnibus GSE166788.
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Hypoxia responseGene expression omnibus GSE2836.
Article and author information
Author details
Funding
National Institutes of Health (R56AG066682)
- Arjumand Ghazi
BC Children's Hospital Foundation
- Stefan Taubert
Natural Sciences and Engineering Research Council of Canada (RGPIN-2018-05133)
- Stefan Taubert
National Institutes of Health (R01AG051659)
- Arjumand Ghazi
Cancer Research Society (22727)
- Stefan Taubert
BC Children's Hospital Foundation
- Kelsie RS Doering
Canada Research Chairs
- Stefan Taubert
National Institutes of Health (R01AG044378)
- Dana L Miller
Natural Sciences and Engineering Research Council of Canada
- Kelsie RS Doering
Canadian Institutes of Health Research (PJT-153199)
- Stefan Taubert
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Douglas Portman, University of Rochester, United States
Version history
- Preprint posted: February 24, 2021 (view preprint)
- Received: February 26, 2021
- Accepted: March 12, 2022
- Accepted Manuscript published: March 14, 2022 (version 1)
- Version of Record published: March 28, 2022 (version 2)
- Version of Record updated: January 5, 2023 (version 3)
Copyright
© 2022, Doering 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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Nuclear Hormone Receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans
eLife 11:e67911.
https://doi.org/10.7554/eLife.67911
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