{"doi":"10.1016/j.isci.2025.112291","title":"Somatic Miwi2 modulates mitochondrial function in airway multiciliated cells and exacerbates influenza pathogenesis","abstract":"MIWI2, a P element-induced wimpy testes (PIWI) argonaute protein known for suppressing retrotransposons during male gonadogenesis, has an unexplored role in mammalian somatic cells. We identify MIWI2 multiciliated (M2MC) cells as a rare subset of airway multiciliated cells and investigate MIWI2's function in antiviral host defense. We analyzed transcriptomes from Miwi2 heterozygous ( Miwi2 +/tom ) and deficient ( Miwi2 tom/tom ) mice following influenza A infection. During infection, Miwi2 deficiency was associated with reduced mitochondrial and ribosomal gene expression in M2MC cells, increased mitochondrial reactive oxygen species (ROS) production and ADP/ATP ratios in multiciliated cells, and enhanced viral clearance and recovery. Additionally, Miwi2 -expressing cells exhibited reduced levels of small RNAs derived from nuclear mitochondrial DNA. These findings reveal a previously unrecognized role for Miwi2 in regulating small non-coding RNAs and mitochondrial oxidant production in somatic cells, indicating a function beyond its established germline activities. Our study identifies Miwi2 / Piwil4 as a potential factor influencing susceptibility to severe respiratory infections.","journal":"iScience","year":2025,"id":540736,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1428762,"name":"Jin Yuan","orcid":"0000-0001-5756-5414","position":1,"is_corresponding":false},{"id":1307013,"name":"Chi Jing Leow","orcid":null,"position":2,"is_corresponding":false},{"id":1281345,"name":"Erin Crossey","orcid":"0000-0001-6058-8406","position":3,"is_corresponding":false},{"id":1086138,"name":"Fengzhi Shao","orcid":null,"position":4,"is_corresponding":false},{"id":1281825,"name":"Senegal Carty","orcid":null,"position":5,"is_corresponding":false},{"id":1429130,"name":"Viviana A. Dominguez","orcid":null,"position":6,"is_corresponding":false},{"id":1047695,"name":"Ming Lo","orcid":"0000-0002-4280-3560","position":7,"is_corresponding":false},{"id":89954,"name":"Joseph P. Mizgerd","orcid":"0000-0002-4042-3169","position":8,"is_corresponding":false},{"id":500879,"name":"Jessica L. Fetterman","orcid":"0000-0002-9286-7538","position":9,"is_corresponding":false},{"id":506723,"name":"Nelson C. Lau","orcid":"0000-0001-9907-1404","position":10,"is_corresponding":false},{"id":1085689,"name":"Alan Fine","orcid":"0000-0001-9351-3048","position":11,"is_corresponding":false},{"id":422671,"name":"Matthew R. Jones","orcid":"0000-0003-4647-2962","position":12,"is_corresponding":false},{"id":1429129,"name":"Jhonatan Henao Vasquez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40241756","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":[]}