{"doi":"10.15252/embj.2020105793","title":"A conserved cysteine‐based redox mechanism sustains TFEB/HLH‐30 activity under persistent stress","abstract":"Mammalian TFEB and TFE3, as well as their ortholog in Caenorhabditis elegans HLH-30, play an important role in mediating cellular response to a variety of stress conditions, including nutrient deprivation, oxidative stress, and pathogen infection. In this study, we identify a novel mechanism of TFEB/HLH-30 regulation through a cysteine-mediated redox switch. Under stress conditions, TFEB-C212 undergoes oxidation, allowing the formation of intermolecular disulfide bonds that result in TFEB oligomerization. TFEB oligomers display increased resistance to mTORC1-mediated inactivation and are more stable under prolonged stress conditions. Mutation of the only cysteine residue present in HLH-30 (C284) significantly reduced its activity, resulting in developmental defects and increased pathogen susceptibility in worms. Therefore, cysteine oxidation represents a new type of TFEB post-translational modification that functions as a molecular switch to link changes in redox balance with expression of TFEB/HLH-30 target genes.","journal":"The EMBO Journal","year":2020,"id":94012,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":469013,"name":"David Guerrero‐Gómez","orcid":"0000-0001-9403-6431","position":1,"is_corresponding":false},{"id":469014,"name":"Eva Gómez‐Orte","orcid":"0000-0001-6802-1746","position":2,"is_corresponding":false},{"id":469015,"name":"José Antonio Bárcena","orcid":"0000-0002-5626-5943","position":3,"is_corresponding":false},{"id":469016,"name":"Juan Cabello","orcid":"0000-0002-3835-0116","position":4,"is_corresponding":false},{"id":469017,"name":"Antonio Miranda‐Vizuete","orcid":"0000-0002-6856-5396","position":5,"is_corresponding":false},{"id":263646,"name":"Rosa Puertollano","orcid":"0000-0002-1106-5489","position":6,"is_corresponding":false},{"id":331603,"name":"José A. Martina","orcid":"0000-0001-5814-8807","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-18T22:32:04.778261Z","pmid":"33314217","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":[]}