{"doi":"10.1016/j.jbc.2021.100929","title":"Resveratrol-induced Sirt1 phosphorylation by LKB1 mediates mitochondrial metabolism","abstract":"-dependent deacetylase Sirt1 has been implicated in the prevention of many age-related diseases, including cancer, type 2 diabetes, and cardiovascular disease. Resveratrol, a plant polyphenol, exhibits antiaging, antitumor, and vascular protection effects by activating Sirt1. However, the molecular mechanism of Sirt1 activation as induced by resveratrol remains unclear. By knockdown/rescue experiments, fluorometric Sirt1 activity assay, immunoprecipitation, and pull-down assays, we identify here that the tumor suppressor LKB1 (liver kinase B1) as a direct activator of Sirt1 elicited by resveratrol. Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. Functionally, LKB1-dependent Sirt1 activation increases mitochondrial biogenesis and respiration through deacetylation and activation of the transcriptional coactivator PGC-1α. These results identify Sirt1 as a context-dependent target of LKB1 and suggest that a resveratrol-stimulated LKB1-Sirt1 pathway plays a vital role in mitochondrial metabolism, a key physiological process that contributes to numerous age-related diseases.","journal":"Journal of Biological Chemistry","year":2021,"id":152927,"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":72,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650442,"name":"Jianlin Lu","orcid":null,"position":1,"is_corresponding":false},{"id":649250,"name":"Zhan Li","orcid":"0000-0001-7748-2691","position":2,"is_corresponding":false},{"id":649251,"name":"Ming Wang","orcid":"0000-0002-7000-1063","position":3,"is_corresponding":false},{"id":649252,"name":"Ronghua Shi","orcid":"0000-0002-4413-3169","position":4,"is_corresponding":false},{"id":649253,"name":"Xiao Yuan","orcid":"0000-0001-6545-6381","position":5,"is_corresponding":false},{"id":649254,"name":"Xinjiao Gao","orcid":"0000-0002-9567-5937","position":6,"is_corresponding":false},{"id":58796,"name":"Xing Liu","orcid":"0000-0002-7480-5085","position":7,"is_corresponding":false},{"id":649255,"name":"Jianye Zang","orcid":"0000-0003-2648-9783","position":8,"is_corresponding":false},{"id":544298,"name":"Wei Liu","orcid":"0000-0003-0696-6407","position":9,"is_corresponding":false},{"id":293205,"name":"Xuebiao Yao","orcid":"0000-0001-8982-5911","position":10,"is_corresponding":false},{"id":649249,"name":"Yuanyuan Huang","orcid":"0000-0001-7718-1637","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-18T23:43:39.820288Z","pmid":"34216621","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":[]}