{"doi":"10.1101/2023.08.09.552390","title":"ULK1-regulated AMP sensing by AMPK and its application for the treatment of chronic kidney disease","abstract":"Abstract AMP-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular adenosine monophosphate (AMP) levels result in AMPK activation through the binding of AMP to the γ-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. In this study, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPKγ1 at Ser260/Thr262 promotes AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1 −/− mice despite an increased AMP/ATP ratio. We also demonstrated that MK8722, an allosteric AMPK activator, activates AMPK in the kidneys of a CKD mouse model via a pathway that is independent of AMP sensing. MK8722 treatment significantly attenuates the deterioration of renal function in CKD and is a potential therapeutic option in CKD therapeutics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400380,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":1036061,"name":"Hiroaki Kikuchi","orcid":"0000-0001-7722-4131","position":1,"is_corresponding":false},{"id":689867,"name":"Koh Takeuchi","orcid":"0000-0002-6227-4627","position":2,"is_corresponding":false},{"id":1034705,"name":"Koichiro Susa","orcid":"0000-0002-0100-4527","position":3,"is_corresponding":false},{"id":746127,"name":"Takayasu Mori","orcid":"0000-0002-9308-7787","position":4,"is_corresponding":false},{"id":1176888,"name":"Naohiro Takahashi","orcid":"0000-0001-9431-9036","position":5,"is_corresponding":false},{"id":966876,"name":"Takefumi Suzuki","orcid":"0000-0002-5147-1684","position":6,"is_corresponding":false},{"id":1176889,"name":"Yuta Nakano","orcid":"0000-0002-6069-066X","position":7,"is_corresponding":false},{"id":1176890,"name":"Tamami Fujiki","orcid":"0000-0002-6697-5930","position":8,"is_corresponding":false},{"id":1176891,"name":"Yu Hara","orcid":"0000-0002-3805-1773","position":9,"is_corresponding":false},{"id":1176892,"name":"Soichiro Suzuki","orcid":"0009-0006-4118-0222","position":10,"is_corresponding":false},{"id":364816,"name":"Yutaro Mori","orcid":"0000-0002-8499-5636","position":11,"is_corresponding":false},{"id":1176893,"name":"Fumiaki Ando","orcid":"0000-0002-8401-1705","position":12,"is_corresponding":false},{"id":1176894,"name":"Shintaro Mandai","orcid":"0000-0001-6709-306X","position":13,"is_corresponding":false},{"id":1176895,"name":"Shinya Honda","orcid":"0000-0003-3443-044X","position":14,"is_corresponding":false},{"id":1176896,"name":"Satoru Torii","orcid":"0000-0003-4841-7131","position":15,"is_corresponding":false},{"id":1136535,"name":"Shigeomi Shimizu","orcid":"0000-0002-8437-0791","position":16,"is_corresponding":false},{"id":1176897,"name":"Tatemitsu Rai","orcid":"0000-0001-7695-778X","position":17,"is_corresponding":false},{"id":500408,"name":"Shinichi Uchida","orcid":null,"position":18,"is_corresponding":false},{"id":1176898,"name":"Eisei Sohara","orcid":"0000-0003-1668-8308","position":19,"is_corresponding":false},{"id":1176887,"name":"Tomoki Yanagi","orcid":"0000-0003-1808-2932","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","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":[]}