Di Zhang, Jinjun Gao, Zhijun Zhu, Qianying Mao, Zhiqiang Xu, Pankaj K. Singh, Cornelius C. Rimayi, Carlos Moreno-Yruela, Shuling Xu, Gongyu Li, Yi-Cheng Sin, Yue Chen, Christian A. Olsen, Nathaniel W. Snyder, Lunzhi Dai, Lingjun Li, Yingming Zhao
{"title":"赖氨酸 l-乳化是糖酵解诱导的主要乳化异构体","authors":"Di Zhang, Jinjun Gao, Zhijun Zhu, Qianying Mao, Zhiqiang Xu, Pankaj K. Singh, Cornelius C. Rimayi, Carlos Moreno-Yruela, Shuling Xu, Gongyu Li, Yi-Cheng Sin, Yue Chen, Christian A. Olsen, Nathaniel W. Snyder, Lunzhi Dai, Lingjun Li, Yingming Zhao","doi":"10.1038/s41589-024-01680-8","DOIUrl":null,"url":null,"abstract":"<p>Lysine <span>l</span>-lactylation (K<sub><span>l</span>-la</sub>) is a novel protein posttranslational modification (PTM) driven by <span>l</span>-lactate. This PTM has three isomers: K<sub><span>l</span>-la</sub>, <i>N</i>-ε-(carboxyethyl)-lysine (K<sub>ce</sub>) and <span>d</span>-lactyl-lysine (K<sub><span>d</span>-la</sub>), 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<sub><span>l</span>-la</sub> is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not K<sub><span>d</span>-la</sub> or K<sub>ce</sub>, which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in <span>l</span>-lactylation, correlates positively with <span>K</span><sub><span>l</span></sub><sub>-la</sub> levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights K<sub><span>l</span>-la</sub> as the primary responder to glycolysis and the Warburg effect.</p><figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":12.9000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lysine l-lactylation is the dominant lactylation isomer induced by glycolysis\",\"authors\":\"Di Zhang, Jinjun Gao, Zhijun Zhu, Qianying Mao, Zhiqiang Xu, Pankaj K. Singh, Cornelius C. Rimayi, Carlos Moreno-Yruela, Shuling Xu, Gongyu Li, Yi-Cheng Sin, Yue Chen, Christian A. Olsen, Nathaniel W. Snyder, Lunzhi Dai, Lingjun Li, Yingming Zhao\",\"doi\":\"10.1038/s41589-024-01680-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Lysine <span>l</span>-lactylation (K<sub><span>l</span>-la</sub>) is a novel protein posttranslational modification (PTM) driven by <span>l</span>-lactate. This PTM has three isomers: K<sub><span>l</span>-la</sub>, <i>N</i>-ε-(carboxyethyl)-lysine (K<sub>ce</sub>) and <span>d</span>-lactyl-lysine (K<sub><span>d</span>-la</sub>), 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<sub><span>l</span>-la</sub> is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not K<sub><span>d</span>-la</sub> or K<sub>ce</sub>, which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in <span>l</span>-lactylation, correlates positively with <span>K</span><sub><span>l</span></sub><sub>-la</sub> levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights K<sub><span>l</span>-la</sub> as the primary responder to glycolysis and the Warburg effect.</p><figure></figure>\",\"PeriodicalId\":18832,\"journal\":{\"name\":\"Nature chemical biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.9000,\"publicationDate\":\"2024-07-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature chemical biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1038/s41589-024-01680-8\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature chemical biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41589-024-01680-8","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Lysine l-lactylation is the dominant lactylation isomer induced by glycolysis
Lysine l-lactylation (Kl-la) is a novel protein posttranslational modification (PTM) driven by l-lactate. This PTM has three isomers: Kl-la, N-ε-(carboxyethyl)-lysine (Kce) and d-lactyl-lysine (Kd-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 Kl-la is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not Kd-la or Kce, 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 Kl-la levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights Kl-la as the primary responder to glycolysis and the Warburg effect.
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