{"doi":"10.1016/j.apsb.2023.10.017","title":"High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice","abstract":"Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.","journal":"Acta Pharmaceutica Sinica B","year":2023,"id":327082,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1047121,"name":"Mengwei Niu","orcid":"0000-0002-3289-725X","position":1,"is_corresponding":false},{"id":288632,"name":"Shaogui Wang","orcid":"0000-0002-2281-6620","position":2,"is_corresponding":false},{"id":648426,"name":"Xiaowen Ma","orcid":"0000-0003-3574-4440","position":3,"is_corresponding":false},{"id":1047122,"name":"Xiao Yang","orcid":"0009-0000-3800-2958","position":4,"is_corresponding":false},{"id":774831,"name":"Hua Sun","orcid":"0000-0003-2851-2086","position":5,"is_corresponding":false},{"id":1047123,"name":"Xujia Hu","orcid":"0000-0002-5320-0941","position":6,"is_corresponding":false},{"id":105553,"name":"Hua Wang","orcid":"0000-0002-2605-5697","position":7,"is_corresponding":false},{"id":444162,"name":"Zhang Li","orcid":"0000-0001-7936-3864","position":8,"is_corresponding":false},{"id":233832,"name":"Ruili Huang","orcid":"0000-0001-8886-8311","position":9,"is_corresponding":false},{"id":355263,"name":"Menghang Xia","orcid":"0000-0001-7285-8469","position":10,"is_corresponding":false},{"id":233334,"name":"Andrea Ballabio","orcid":"0000-0003-1381-4604","position":11,"is_corresponding":false},{"id":267071,"name":"Hartmut Jaeschke","orcid":"0000-0002-8695-6980","position":12,"is_corresponding":false},{"id":284311,"name":"Hong‐Min Ni","orcid":"0000-0002-5300-2654","position":13,"is_corresponding":false},{"id":284312,"name":"Wen‐Xing Ding","orcid":"0000-0002-3167-5073","position":14,"is_corresponding":false},{"id":284307,"name":"Xiaojuan Chao","orcid":"0000-0002-8731-7785","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:08:42.846627Z","pmid":"38261809","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":[]}