{"doi":"10.1073/pnas.2403392121","title":"MAVS Cys508 palmitoylation promotes its aggregation on the mitochondrial outer membrane and antiviral innate immunity","abstract":"Cysteine palmitoylation or S -palmitoylation catalyzed by the ZDHHC family of acyltransferases regulates the biological function of numerous mammalian proteins as well as viral proteins. However, understanding of the role of S -palmitoylation in antiviral immunity against RNA viruses remains very limited. The adaptor protein MAVS forms functionally essential prion-like aggregates upon activation by viral RNA-sensing RIG-I-like receptors. Here, we identify that MAVS, a C-terminal tail-anchored mitochondrial outer membrane protein, is S -palmitoylated by ZDHHC7 at Cys508, a residue adjacent to the tail-anchor transmembrane helix. Using superresolution microscopy and other biochemical techniques, we found that the mitochondrial localization of MAVS at resting state mainly depends on its transmembrane tail-anchor, without regulation by Cys508 S -palmitoylation. However, upon viral infection, MAVS S -palmitoylation stabilizes its aggregation on the mitochondrial outer membrane and thus promotes subsequent propagation of antiviral signaling. We further show that inhibition of MAVS S -palmitoylation increases the host susceptibility to RNA virus infection, highlighting the importance of S -palmitoylation in the antiviral innate immunity. Also, our results indicate ZDHHC7 as a potential therapeutic target for MAVS-related autoimmune diseases.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":421672,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":895918,"name":"Dan Hou","orcid":"0009-0003-9501-4180","position":1,"is_corresponding":false},{"id":1214573,"name":"Wenzhe Chen","orcid":"0000-0002-0758-1237","position":2,"is_corresponding":false},{"id":885871,"name":"Xuan Lü","orcid":"0000-0003-4886-0918","position":3,"is_corresponding":false},{"id":277252,"name":"Garrison Komaniecki","orcid":"0000-0002-1157-2667","position":4,"is_corresponding":false},{"id":1215190,"name":"Yilai Xu","orcid":null,"position":5,"is_corresponding":false},{"id":14845,"name":"Tao Yu","orcid":"0000-0001-7896-4625","position":6,"is_corresponding":false},{"id":27181,"name":"S. Zhang","orcid":"0000-0002-8480-2662","position":7,"is_corresponding":false},{"id":384912,"name":"Maurine E. Linder","orcid":"0000-0003-2202-9712","position":8,"is_corresponding":false},{"id":273804,"name":"Hening Lin","orcid":"0000-0002-0255-2701","position":9,"is_corresponding":false},{"id":1214572,"name":"Yinong Liu","orcid":"0009-0009-0405-5686","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T01:57:41.370244Z","pmid":"39141356","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":[]}