{"doi":"10.1016/j.celrep.2023.112807","title":"Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery","abstract":"Cellular homeostasis relies on both the chaperoning of proteins and the intracellular degradation system that delivers cytoplasmic constituents to the lysosome, a process known as autophagy. The crosstalk between these processes and their underlying regulatory mechanisms is poorly understood. Here, we show that the molecular chaperone heat shock protein 90 (Hsp90) forms a complex with the autophagy-initiating kinase Atg1 (yeast)/Ulk1 (mammalian), which suppresses its kinase activity. Conversely, environmental cues lead to Atg1/Ulk1-mediated phosphorylation of a conserved serine in the amino domain of Hsp90, inhibiting its ATPase activity and altering the chaperone dynamics. These events impact a conformotypic peptide adjacent to the activation and catalytic loop of Atg1/Ulk1. Finally, Atg1/Ulk1-mediated phosphorylation of Hsp90 leads to dissociation of the Hsp90:Atg1/Ulk1 complex and activation of Atg1/Ulk1, which is essential for initiation of autophagy. Our work indicates a reciprocal regulatory mechanism between the chaperone Hsp90 and the autophagy kinase Atg1/Ulk1 and consequent maintenance of cellular proteostasis.","journal":"Cell Reports","year":2023,"id":324350,"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":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"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":349164,"name":"Rebecca Sager","orcid":null,"position":1,"is_corresponding":false},{"id":1041026,"name":"Jennifer A. Heritz","orcid":null,"position":2,"is_corresponding":false},{"id":1041027,"name":"Laura A. Wengert","orcid":null,"position":3,"is_corresponding":false},{"id":945520,"name":"Katherine A. Meluni","orcid":null,"position":4,"is_corresponding":false},{"id":1040396,"name":"Xavier Aran-Guiu","orcid":"0000-0003-4683-6340","position":5,"is_corresponding":false},{"id":142420,"name":"Barry Panaretou","orcid":null,"position":6,"is_corresponding":false},{"id":346994,"name":"Mark R. Woodford","orcid":"0000-0002-6737-2832","position":7,"is_corresponding":false},{"id":347000,"name":"Chrisostomos Prodromou","orcid":"0000-0003-4320-1147","position":8,"is_corresponding":false},{"id":346998,"name":"Dimitra Bourboulia","orcid":"0000-0002-8567-2775","position":9,"is_corresponding":false},{"id":347006,"name":"Mehdi Mollapour","orcid":"0000-0002-2144-1361","position":10,"is_corresponding":false},{"id":346995,"name":"Sarah J. Backe","orcid":"0000-0001-9275-267X","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-19T01:08:11.275604Z","pmid":"37453059","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":[]}