{"doi":"10.7554/elife.67911","title":"Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans","abstract":"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.","journal":"eLife","year":2022,"id":246778,"datarank":0.8863676583555791,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.3447299714589454,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.3447299714589454,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":28,"citers_with_citation_signal":18,"citers_with_endowment":18,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE166788","GSE2836"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":824747,"name":"Xuanjin Cheng","orcid":"0000-0002-2119-1788","position":1,"is_corresponding":false},{"id":825246,"name":"Luke Milburn","orcid":null,"position":2,"is_corresponding":false},{"id":380505,"name":"Ramesh Ratnappan","orcid":"0000-0001-7055-9043","position":3,"is_corresponding":false},{"id":392144,"name":"Arjumand Ghazi","orcid":"0000-0002-5859-4206","position":4,"is_corresponding":false},{"id":824748,"name":"Dana L. Miller","orcid":"0000-0003-3983-0493","position":5,"is_corresponding":false},{"id":295630,"name":"Stefan Taubert","orcid":"0000-0002-2432-7257","position":6,"is_corresponding":false},{"id":824746,"name":"Kelsie R. S. Doering","orcid":"0000-0003-3485-7419","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T00:23:48.622830Z","pmid":"35285794","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}