{"doi":"10.1038/s41589-024-01680-8","title":"Lysine l-lactylation is the dominant lactylation isomer induced by glycolysis","abstract":"Abstract Lysine l -lactylation (K l -la ) is a novel protein posttranslational modification (PTM) driven by l -lactate. This PTM has three isomers: K l -la , N -ε-(carboxyethyl)-lysine (K ce ) and d -lactyl-lysine (K d -la ), which are often confused in the context of the Warburg effect and nuclear presence. Here we introduce two methods to differentiate these isomers: a chemical derivatization and high-performance liquid chromatography analysis for efficient separation, and isomer-specific antibodies for high-selectivity identification. We demonstrated that K l -la is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not K d -la or K ce , which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in l -lactylation, correlates positively with K l -la levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights K l -la as the primary responder to glycolysis and the Warburg effect.","journal":"Nature Chemical Biology","year":2024,"id":416399,"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":148,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":659559,"name":"Jinjun Gao","orcid":"0000-0002-7390-5578","position":1,"is_corresponding":false},{"id":1128858,"name":"Zhijun Zhu","orcid":"0009-0002-9465-498X","position":2,"is_corresponding":false},{"id":1200652,"name":"Qian‐Ying Mao","orcid":null,"position":3,"is_corresponding":false},{"id":829630,"name":"Zhiqiang Xu","orcid":null,"position":4,"is_corresponding":false},{"id":1133458,"name":"Pankaj Kumar Singh","orcid":"0000-0001-9626-5182","position":5,"is_corresponding":false},{"id":1139991,"name":"Cornelius Rimayi","orcid":"0000-0002-5494-7094","position":6,"is_corresponding":false},{"id":74835,"name":"Carlos Moreno-Yruela","orcid":"0000-0003-2450-6519","position":7,"is_corresponding":false},{"id":1199636,"name":"Shuling Xu","orcid":"0009-0005-3294-4537","position":8,"is_corresponding":false},{"id":588183,"name":"Gongyu Li","orcid":"0000-0002-2367-4433","position":9,"is_corresponding":false},{"id":1199637,"name":"Yi-Cheng Sin","orcid":"0000-0002-9876-9197","position":10,"is_corresponding":false},{"id":382599,"name":"Yue Chen","orcid":"0000-0002-0153-9927","position":11,"is_corresponding":false},{"id":90538,"name":"Christian A. Olsen","orcid":"0000-0002-2953-8942","position":12,"is_corresponding":false},{"id":237765,"name":"Nathaniel W. Snyder","orcid":"0000-0001-5643-8747","position":13,"is_corresponding":false},{"id":114543,"name":"Lunzhi Dai","orcid":"0000-0002-3003-8910","position":14,"is_corresponding":false},{"id":289711,"name":"Lingjun Li","orcid":"0000-0003-0056-3869","position":15,"is_corresponding":false},{"id":225713,"name":"Yingming Zhao","orcid":"0000-0003-1928-2151","position":16,"is_corresponding":false},{"id":621870,"name":"Di Zhang","orcid":"0000-0002-9341-9884","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:56:20.964471Z","pmid":"39030363","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":[]}