{"doi":"10.1016/j.scitotenv.2023.167315","title":"Mitochondrial DNA release mediated by TFAM deficiency promotes copper-induced mitochondrial innate immune response via cGAS-STING signalling in chicken hepatocytes","abstract":null,"journal":"Science of The Total Environment","year":2023,"id":601176,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1541377,"name":"Shaofeng Wang","orcid":null,"position":1,"is_corresponding":false},{"id":1541378,"name":"Pan Guo","orcid":null,"position":2,"is_corresponding":false},{"id":1541379,"name":"Yuanhong Feng","orcid":null,"position":3,"is_corresponding":false},{"id":905262,"name":"Wenlan Yu","orcid":"0000-0002-7366-3230","position":4,"is_corresponding":false},{"id":1416232,"name":"Hui Zhang","orcid":"0000-0002-4442-2788","position":5,"is_corresponding":false},{"id":1541380,"name":"Jianying Guo","orcid":null,"position":6,"is_corresponding":false},{"id":782936,"name":"Ying Li","orcid":"0000-0002-8029-0399","position":7,"is_corresponding":false},{"id":1541381,"name":"Lianmei Hu","orcid":null,"position":8,"is_corresponding":false},{"id":1541382,"name":"Jiaqiang Pan","orcid":null,"position":9,"is_corresponding":false},{"id":1541383,"name":"Jianzhao Liao","orcid":null,"position":10,"is_corresponding":false},{"id":1541384,"name":"Zhaoxin Tang","orcid":null,"position":11,"is_corresponding":false},{"id":1541376,"name":"Quanwei Li","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mitochondrial DNA release mediated by TFAM deficiency promotes copper-induced mitochondrial innate immune response via cGAS-STING signalling in chicken hepatocytes","abstract":"Copper (Cu) is pollution metal that is a global concern due to its toxic effects. A recent study found that the release of mitochondrial DNA (mtDNA) into the cytoplasm can activate the innate immune response, but the exact mechanisms underlying the effect of Cu exposure remains unknown. In this study, we identified that the reduction in transcription Factor A (TFAM) led to mtDNA leakage into the cytoplasm under Cu exposure in hepatocytes, accompanied by the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway-mediated innate immunity (increased expression of cGAS, STING, TANK-binding kinase-1 (TBK1), and interferon regulatory factor-3 (IRF3)) genes and proteins, and enhanced phosphorylation levels of TBK1 and IRF3). Subsequently, silencing TFAM (siTFAM) significantly aggravated mtDNA release and the innate immune response under Cu treatment. Mitochondrial DNA depletion alleviated Cu-induced innate immunity in hepatocytes, while mtDNA transfection further enhanced the innate immune response. Notably, the inhibition of STING effectively alleviated the phosphorylation levels of the TBK1 and IRF3 proteins induced by Cu, while the upregulation of STING aggravated the Cu-induced innate immunity. Furthermore, EtBr and H-151(a STING inhibitor) treatment dramatically reversed the effect of TFAM depletion on the sharpened innate immune response induced by Cu via the cGAS-STING pathway. In general, these findings demonstrated the TFAM deficiency promotes innate immunity by activating the mtDNA-cGAS-STING signalling pathway under Cu exposure in hepatocytes, providing new insight into Cu toxicology.","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37742962","pmcid":null,"openalex_id":"https://openalex.org/W4386946039","authors":[],"funders":[{"funder_name":"Natural Science Foundation of Guangdong Province","grant_id":"2023A1515012811","title":null},{"funder_name":"Natural Science Foundation of Guangdong Province","grant_id":"2022A1515110090","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"32072930","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"31572585","title":null}],"total_grants":4,"fwci":1.9306,"citation_percentile":0.8716112,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":5},{"year":2025,"count":4},{"year":2026,"count":11}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0048969723059429?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0048969723059429?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.scitotenv.2023.167315","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37742962","host_type":"repository"}],"fields_of_study":["interferon and immune responses","Viral Infections and Vectors","Immune Response and Inflammation","Animals","Avian Proteins","Chickens","Copper","DNA, Mitochondrial","Hepatocytes","Immunity, Innate","Membrane Proteins","Mitochondrial Proteins","Nucleotidyltransferases","Transcription Factors"],"mesh_terms":["Animals","Chickens","Copper","DNA, Mitochondrial","Immunity, Innate","Membrane Proteins","Nucleotidyltransferases","Transcription Factors","Hepatocytes","Mitochondrial Proteins","Avian Proteins"],"keywords":["IRF3","Innate immune system","TFAM","Stimulator of interferon genes","Biology","Cell biology","TANK-binding kinase 1","Interferon","Mitochondrial DNA","Mitochondrion","Phosphorylation","Immune system","Immunology","Protein kinase A","Biochemistry","Mitochondrial biogenesis","Gene","Copper","innate immune response","Cgas-sting Pathway"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T15:20:55.380977Z","pmid":null,"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":[]}