Lysine l-lactylation is the dominant lactylation isomer induced by glycolysis

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…

• NS
  National Science Foundation

  Awards: 2108223, CHE-2108223
• UO
  University of Chicago
• EC
  European Commission

  Award: 725172
• NN
  National Natural Science Foundation of China

  Award: 32270822
• PU
  Peking University
• NI
  National Institutes of Health

  Awards: CA251677, AR078555, S10RR029531, DK071801, S10OD028473
• UO
  University of Texas MD Anderson Cancer Center
• UO
  University of California, San Diego
• WC
  West China Hospital, Sichuan University

  Award: ZYJC21005
• DO
  Division of Chemistry

  Awards: CHE-2108223, 2108223