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Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans
The response to insufficient oxygen (hypoxia) is orchestrated by the conserved hypoxia-inducible factor (HIF). However, HIF-independent hypoxia response pathways exist that act in parallel with HIF to mediate the physiological hypoxia response. Here, we describe a hypoxia response pathway controlled...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959602/ https://www.ncbi.nlm.nih.gov/pubmed/35285794 http://dx.doi.org/10.7554/eLife.67911 |
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author | Doering, Kelsie RS Cheng, Xuanjin Milburn, Luke Ratnappan, Ramesh Ghazi, Arjumand Miller, Dana L Taubert, Stefan |
author_facet | Doering, Kelsie RS Cheng, Xuanjin Milburn, Luke Ratnappan, Ramesh Ghazi, Arjumand Miller, Dana L Taubert, Stefan |
author_sort | Doering, Kelsie RS |
collection | PubMed |
description | The response to insufficient oxygen (hypoxia) is orchestrated by the conserved hypoxia-inducible factor (HIF). However, HIF-independent hypoxia response pathways exist that act in parallel with HIF to mediate the physiological hypoxia response. Here, we describe a hypoxia response pathway controlled by 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. |
format | Online Article Text |
id | pubmed-8959602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-89596022022-03-29 Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans Doering, Kelsie RS Cheng, Xuanjin Milburn, Luke Ratnappan, Ramesh Ghazi, Arjumand Miller, Dana L Taubert, Stefan eLife Chromosomes and Gene Expression The response to insufficient oxygen (hypoxia) is orchestrated by the conserved hypoxia-inducible factor (HIF). However, HIF-independent hypoxia response pathways exist that act in parallel with HIF to mediate the physiological hypoxia response. Here, we describe a hypoxia response pathway controlled by 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. eLife Sciences Publications, Ltd 2022-03-14 /pmc/articles/PMC8959602/ /pubmed/35285794 http://dx.doi.org/10.7554/eLife.67911 Text en © 2022, Doering et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Chromosomes and Gene Expression Doering, Kelsie RS Cheng, Xuanjin Milburn, Luke Ratnappan, Ramesh Ghazi, Arjumand Miller, Dana L Taubert, Stefan Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans |
title | Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans |
title_full | Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans |
title_fullStr | Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans |
title_full_unstemmed | Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans |
title_short | Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans |
title_sort | nuclear hormone receptor nhr-49 acts in parallel with hif-1 to promote hypoxia adaptation in caenorhabditis elegans |
topic | Chromosomes and Gene Expression |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959602/ https://www.ncbi.nlm.nih.gov/pubmed/35285794 http://dx.doi.org/10.7554/eLife.67911 |
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