Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

The emerging role of protein l-lactylation in metabolic regulation and cell signalling

Nature Metabolism volume 7, pages 647–664 (2025)Cite this article

Subjects

Abstract

l-Lactate has emerged as a crucial metabolic intermediate, moving beyond its traditional view as a mere waste product. The recent discovery of l-lactate-driven protein lactylation as a post-translational modification has unveiled a pathway that highlights the role of lactate in cellular signalling. In this Perspective, we explore the enzymatic and metabolic mechanisms underlying protein lactylation and its impacts on both histone and non-histone proteins in the contexts of physiology and diseases. We discuss growing evidence suggesting that this modification regulates a wide range of cellular functions and is involved in various physiological and pathological processes, such as cell-fate determination, development, cardiovascular diseases, cancer and autoimmune disorders. We propose that protein lactylation acts as a pivotal mechanism, integrating metabolic and signalling pathways to enable cellular adaptation, and highlight its potential as a therapeutic target in various diseases.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The biochemistry of protein lactylation.
Fig. 2: Regulation of DNA activity by protein lactylation.
Fig. 3: Regulation of cell metabolism and signalling by protein lactylation.
Fig. 4: Protein lactylation in cardiovascular diseases.
Fig. 5: Protein lactylation in tumours.
Fig. 6: Protein lactylation in autoimmune uveitis.

Similar content being viewed by others

References

  1. Warburg, O., Wind, F. & Negelein, E. The metabolism of tumors in the body. J. Gen. Physiol. 8, 519–530 (1927).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Adeva-Andany, M. et al. Comprehensive review on lactate metabolism in human health. Mitochondrion 17, 76–100 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Rabinowitz, J. D. & Enerback, S. Lactate: the ugly duckling of energy metabolism. Nat. Metab. 2, 566–571 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Brooks, G. A. et al. Lactate in contemporary biology: a phoenix risen. J. Physiol. 600, 1229–1251 (2022).

    Article  CAS  PubMed  Google Scholar 

  5. Certo, M. et al. Lactate modulation of immune responses in inflammatory versus tumour microenvironments. Nat. Rev. Immunol. 21, 151–161 (2021).

    Article  CAS  PubMed  Google Scholar 

  6. Li, X. et al. Lactate metabolism in human health and disease. Signal. Transduct. Target Ther. 7, 305 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Houtkooper, R. H., Canto, C., Wanders, R. J. & Auwerx, J. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 31, 194–223 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. Ahmed, K. et al. An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab. 11, 311–319 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Daw, C. C. et al. Lactate elicits ER-mitochondrial Mg2+ dynamics to integrate cellular metabolism. Cell 183, 474–489 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Liu, W. et al. Lactate regulates cell cycle by remodelling the anaphase promoting complex. Nature 616, 790–797 (2023).

    Article  CAS  PubMed  Google Scholar 

  11. Cai, X. et al. Lactate activates the mitochondrial electron transport chain independently of its metabolism. Mol. Cell 83, 3904–3920 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–57 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ramazi, S. & Zahiri, J. Post-translational modifications in proteins: resources, tools and prediction methods. Database 2021, baab012 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Walsh, C. T., Garneau-Tsodikova, S. & Gatto, G. J. Jr. Protein posttranslational modifications: the chemistry of proteome diversifications. Angew Chem. Int. Ed. Engl. 44, 7342–7372 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Su, X. Y., Wellen, K. E. & Rabinowitz, J. D. Metabolic control of methylation and acetylation. Curr. Opin. Chem. Biol. 30, 52–60 (2016).

    Article  CAS  PubMed  Google Scholar 

  16. Choudhary, C. et al. The growing landscape of lysine acetylation links metabolism and cell signalling. Nat. Rev. Mol. Cell Biol. 15, 536–550 (2014).

    Article  CAS  PubMed  Google Scholar 

  17. Sabari, B. R., Zhang, D., Allis, C. D. & Zhao, Y. Metabolic regulation of gene expression through histone acylations. Nat. Rev. Mol. Cell Biol. 18, 90–101 (2017).

    Article  CAS  PubMed  Google Scholar 

  18. Dai, Z., Ramesh, V. & Locasale, J. W. The evolving metabolic landscape of chromatin biology and epigenetics. Nat. Rev. Genet. 21, 737–753 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gaffney, D. O. et al. Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell Chem. Biol. 27, 206–213 (2020).

    Article  CAS  PubMed  Google Scholar 

  20. Ahmed, M. U. et al. N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem. J 324, 565–570 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang, D. et al. Lysine l-lactylation is the dominant lactylation isomer induced by glycolysis. Nat. Chem. Biol. 21, 91–99 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gao, J. et al. Identification of 113 new histone marks by CHiMA, a tailored database search strategy. Sci. Adv. 9, eadf1416 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang, D. et al. Identification of lysine-lactylated substrates in gastric cancer cells. iScience 25, 104630 (2022).

    CAS  Google Scholar 

  24. Wang, X. et al. YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2. Genome Biol. 24, 87 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yang, Y. H. et al. Global profiling of lysine lactylation in human lungs. Proteomics 23, e2200437 (2023).

    Article  PubMed  Google Scholar 

  26. Lin, Y. et al. Multi-proteomic analysis reveals the effect of protein lactylation on matrix and cholesterol metabolism in tendinopathy. J. Proteom. Res. 22, 1712–1722 (2023).

    Article  CAS  Google Scholar 

  27. Yang, Z. et al. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat. Metab. 5, 61–79 (2023).

    Article  CAS  PubMed  Google Scholar 

  28. Yao, Y. et al. Global-scale profiling of differential expressed lysine-lactylated proteins in the cerebral endothelium of cerebral ischemia-reperfusion injury rats. Cell Mol. Neurobiol. 43, 1989–2004 (2023).

    Article  CAS  PubMed  Google Scholar 

  29. Zhang, N. et al. Protein lactylation critically regulates energy metabolism in the protozoan parasite Trypanosoma brucei. Front. Cell Dev. Biol. 9, 719720 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Yin, D. et al. Protein lactylation and metabolic regulation of the zoonotic parasite Toxoplasma gondii. Genomics Proteomics Bioinformatics 21, 1163–1181 (2023).

    Article  CAS  PubMed  Google Scholar 

  31. An, D. et al. Comprehensive analysis of lysine lactylation in Frankliniella occidentalis. Front. Genet. 13, 1014225 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhao, W. et al. Systematic identification of the lysine lactylation in the protozoan parasite Toxoplasma gondii. Parasit. Vectors 15, 180 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Song, Y. G. et al. Post-translational changes in lysine lactylation during prolonged presence in a patient with a related immune disorder. Front. Immunol. 13, 966457 (2022).

  34. Meng, X., Baine, J. M., Yan, T. & Wang, S. Comprehensive analysis of lysine lactylation in rice (Oryza sativa) grains. J. Agric. Food Chem. 69, 8287–8297 (2021).

    Article  CAS  PubMed  Google Scholar 

  35. Wu, Q. et al. Deciphering the atlas of post-translational modification in sugarcane. J. Agric. Food Chem. 71, 10004–10017 (2023).

    Article  CAS  PubMed  Google Scholar 

  36. Hansen, B. K. et al. Analysis of human acetylation stoichiometry defines mechanistic constraints on protein regulation. Nat. Commun. 10, 1055 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Olsen, J. V. et al. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal 3, ra3 (2010).

    Article  PubMed  Google Scholar 

  38. Prus, G. et al. Global, site-resolved analysis of ubiquitylation occupancy and turnover rate reveals systems properties. Cell 187, 2875–2892 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Allis, C. D. et al. New nomenclature for chromatin-modifying enzymes. Cell 131, 633–636 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Wang, N. et al. Histone lactylation boosts reparative gene activation post-myocardial infarction. Circ. Res. 131, 893–908 (2022).

    Article  CAS  PubMed  Google Scholar 

  41. Zhu, R. et al. ACSS2 acts as a lactyl-CoA synthetase and couples KAT2A to function as a lactyltransferase for histone lactylation and tumor immune evasion. Cell Metab. 37, 361–376 (2024).

    Article  PubMed  Google Scholar 

  42. Chen, Y. et al. Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell 187, 294–311 (2024).

    Article  CAS  PubMed  Google Scholar 

  43. Chen, H. X. et al. NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature 631, 663–669 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Niu, Z. et al. HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription. Nat. Commun. 15, 3561 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Xie, B. et al. KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proc. Natl Acad. Sci. USA 121, e2314128121 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wang, Y. G. et al. KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase. Nature 552, 273–27 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu, R. et al. Nuclear GTPSCS functions as a lactyl-CoA synthetase to promote histone lactylation and gliomagenesis. Cell Metab. 37, 377–394 (2024).

    Article  PubMed  Google Scholar 

  48. Ibba, M. & Soll, D. Aminoacyl-tRNA synthesis. Annu. Rev. Biochem. 69, 617–650 (2000).

    Article  CAS  PubMed  Google Scholar 

  49. Mao, Y. et al. Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation. Cell Res. 34, 13–30 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ju, J. Y. et al. The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. J. Clin. Invest. 134, e174587 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zong, Z. et al. Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell 187, 2375–2392 (2024).

    Article  CAS  PubMed  Google Scholar 

  52. Sun, L. H. et al. Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer. Nat. Commun. 14, 6523 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Li, H. et al. AARS1 and AARS2 sense l-lactate to regulate cGAS as global lysine lactyltransferases. Nature. 634 1229–1237 (2024).

    Article  CAS  PubMed  Google Scholar 

  54. Seto, E. & Yoshida, M. Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb. Perspect. Biol. 6, a018713 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lahm, A. et al. Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc. Natl Acad. Sci. USA 104, 17335–17340 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Du, J. T. et al. Sirt5 Is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334, 806–809 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Peng, C. et al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell Proteomics 10, M111.012658 (2011).

  58. Tan, M. J. et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 19, 605–617 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kutil, Z. et al. Histone deacetylase 11 is a fatty-acid deacylase. ACS Chem. Biol. 13, 685–693 (2018).

    Article  CAS  PubMed  Google Scholar 

  60. Moreno-Yruela, C., Galleano, I., Madsen, A. S. & Olsen, C. A. Histone deacetylase 11 is an ε-N-myristoyllysine hydrolase. Cell Chem. Biol. 25, 849–84 (2018).

    Article  CAS  PubMed  Google Scholar 

  61. Madsen, A. S. & Olsen, C. A. Profiling of substrates for zinc-dependent lysine deacylase enzymes: HDAC3 exhibits decrotonylase activity in vitro. Angew. Chem. Int. Ed. Engl. 51, 9083–9087 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Wei, W. et al. Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription. Cell Res. 27, 898–915 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Huang, H. et al. The regulatory enzymes and protein substrates for the lysine beta-hydroxybutyrylation pathway. Sci. Adv. 7, eabe2771 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Moreno-Yruela, C. et al. Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci. Adv. 8, eabi6696 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zessin, M. et al. Uncovering robust delactoylase and depyruvoylase activities of HDAC isoforms. ACS Chem. Biol. 17, 1364–1375 (2022).

    Article  CAS  PubMed  Google Scholar 

  66. Wang, Z. A. et al. Histone H2B deacylation selectivity: exploring chromatin’s dark matter with an engineered Sortase. J. Am. Chem. Soc. 144, 3360–3364 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Du, R. et al. Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis. iScience 27, 110911 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Jin, J. et al. SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth. EMBO Rep. 24, e56052 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fan, Z. M. et al. Identification of SIRT3 as an eraser of H4K16la. iScience 26, 107757 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yun, M., Wu, J., Workman, J. L. & Li, B. Readers of histone modifications. Cell Res. 21, 564–578 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Andrews, F. H., Strahl, B. D. & Kutateladze, T. G. Insights into newly discovered marks and readers of epigenetic information. Nat. Chem. Biol. 12, 662–668 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Dhalluin, C. et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491–496 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. Nunez, R. et al. The TRIM33 bromodomain recognizes histone lysine lactylation. ACS Chem. Biol. 19, 2418–2428 (2024).

    Article  CAS  PubMed  Google Scholar 

  74. Ferri, F. et al. TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation. Nat. Commun. 6, 8900 (2015).

    Article  CAS  PubMed  Google Scholar 

  75. Palsson-McDermott, E. M. & O’Neill, L. A. J. The Warburg effect then and now: from cancer to inflammatory diseases. Bioessays 35, 965–973 (2013).

    Article  CAS  PubMed  Google Scholar 

  76. Phillips, D. M. The presence of acetyl groups of histones. Biochem. J 87, 258–263 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Allfrey, V. G., Faulkner, R. & Mirsky, A. E. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl Acad. Sci. USA 51, 786–794 (1964).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Guarente, L. The logic linking protein acetylation and metabolism. Cell Metab. 14, 151–153 (2011).

    Article  CAS  PubMed  Google Scholar 

  79. Bose, S., Ramesh, V. & Locasale, J. W. Acetate metabolism in physiology, cancer, and beyond. Trends Cell Biol. 29, 695–703 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Guertin, D. A. & Wellen, K. E. Acetyl-CoA metabolism in cancer. Nat. Rev. Cancer 23, 156–172 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kelly, B. & O’Neill, L. A. Metabolic reprogramming in macrophages and dendritic cells in innate immunity. Cell Res. 25, 771–784 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Sung, E. et al. Global profiling of lysine acetylation and lactylation in Kupffer cells. J. Proteome Res. 22, 3683–3691 (2023).

    Article  CAS  PubMed  Google Scholar 

  83. Sun, S. et al. Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed alpha-tubulin lactylation. Nat. Commun. 15, 8377 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Campbell, S. L. & Wellen, K. E. Metabolic signaling to the nucleus in cancer. Mol. Cell 71, 398–408 (2018).

    CAS  Google Scholar 

  85. Wellen, K. E. & Thompson, C. B. A two-way street: reciprocal regulation of metabolism and signalling. Nat. Rev. Mol. Cell Biol. 13, 270–276 (2012).

    Article  CAS  PubMed  Google Scholar 

  86. Hagihara, H. et al. Protein lactylation induced by neural excitation. Cell Rep. 37, 109820 (2021).

    Article  CAS  PubMed  Google Scholar 

  87. Wright, W. D., Shah, S. S. & Heyer, W. D. Homologous recombination and the repair of DNA double-strand breaks. J. Biol. Chem. 293, 10524–10535 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Li, G. et al. Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma. Cell Metab. 36, 1696–1710 (2024).

    Article  CAS  PubMed  Google Scholar 

  89. Wan, N. et al. Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome. Nat. Methods 19, 854–864 (2022).

    Article  CAS  PubMed  Google Scholar 

  90. Meng, Q. et al. Human papillomavirus-16 E6 activates the pentose phosphate pathway to promote cervical cancer cell proliferation by inhibiting G6PD lactylation. Redox. Biol. 71, 103108 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Jia, M. et al. ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation. Sci. Adv. 9, eadg4993 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Folmes, C. D. & Terzic, A. Metabolic determinants of embryonic development and stem cell fate. Reprod. Fertil. Dev. 27, 82–88 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Ryall, J. G., Cliff, T., Dalton, S. & Sartorelli, V. Metabolic reprogramming of stem cell epigenetics. Cell Stem Cell 17, 651–662 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ito, K. & Suda, T. Metabolic requirements for the maintenance of self-renewing stem cells. Nat. Rev. Mol. Cell Biol. 15, 243–256 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Gatie, M. I. et al. Lactate enhances mouse ES cell differentiation toward XEN cells in vitro. Stem Cells 40, 239–259 (2022).

    Article  PubMed  Google Scholar 

  96. Dong, Q. et al. Glycolysis-stimulated Esrrb lactylation promotes the self-renewal and extraembryonic endoderm stem cell differentiation of embryonic stem cells. Int. J. Mol. Sci. 25, 2692 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Panopoulos, A. D. et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 22, 168–177 (2012).

    Article  CAS  PubMed  Google Scholar 

  98. Folmes, C. D. L. et al. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 14, 264–271 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Li, L. et al. Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade. Nat. Metab. 2, 882–892 (2020).

    Article  CAS  PubMed  Google Scholar 

  100. Hu, X. L. et al. Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader. Nucleic Acids Res. 52, 5529–5548 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Schulz, K. N. & Harrison, M. M. Mechanisms regulating zygotic genome activation. Nat. Rev. Genet. 20, 221–234 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Li, J. et al. Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals. Natl Sci. Rev. 11, nwad295 (2024).

    Article  CAS  PubMed  Google Scholar 

  103. Oginuma, M. et al. A gradient of glycolytic activity coordinates FGF and Wnt signaling during elongation of the body axis in amniote embryos. Dev. Cell 40, 342–353 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Bhattacharya, D., Azambuja, A. P. & Simoes-Costa, M. Metabolic reprogramming promotes neural crest migration via Yap/Tead signaling. Dev. Cell 53, 199–211 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Merkuri, F., Rothstein, M. & Simoes-Costa, M. Histone lactylation couples cellular metabolism with developmental gene regulatory networks. Nat. Commun. 15, 90 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Govindarajan, G. et al. The cardiometabolic syndrome as a cardiovascular risk factor. Am. J. Med. Sci. 330, 311–318 (2005).

    Article  PubMed  Google Scholar 

  107. Zhu, W. et al. Lactate and lactylation in cardiovascular diseases: current progress and future perspectives. Metabolism 158, 155957 (2024).

    Article  CAS  PubMed  Google Scholar 

  108. Murashige, D. et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science 370, 364–368 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Zhang, N. et al. Alpha-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure. Cell Res. 33, 679–698 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. De Bock, K. et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154, 651–663 (2013).

    Article  PubMed  Google Scholar 

  111. Li, Y., Lui, K. O. & Zhou, B. Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases. Nat. Rev. Cardiol. 15, 445–456 (2018).

    Article  PubMed  Google Scholar 

  112. Fan, M. et al. Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction. Sci. Adv. 9, eadc9465 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    Article  CAS  PubMed  Google Scholar 

  114. Warburg, O. On the origin of cancer cells. Science 123, 309–314 (1956).

    Article  CAS  PubMed  Google Scholar 

  115. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324, 1029–1033 (2009).

    Article  Google Scholar 

  116. Liberti, M. V. & Locasale, J. W. The Warburg effect: how does it benefit cancer cells? Trends Biochem. Sci. 41, 211–218 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Noman, M. Z. et al. Hypoxia: a key player in antitumor immune response. A review in the theme: cellular responses to hypoxia. Am. J. Physiol. Cell Physiol. 309, C569–C579 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Chu, Y. D. et al. Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect. Cell Death Dis. 14, 660 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Zhou, J. et al. GPR37 promotes colorectal cancer liver metastases by enhancing the glycolysis and histone lactylation via Hippo pathway. Oncogene 42, 3319–3330 (2023).

    Article  CAS  PubMed  Google Scholar 

  120. Li, W. H. et al. Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy 20, 114–130 (2024).

    Article  CAS  PubMed  Google Scholar 

  121. Sun, X. et al. The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity. Cell Metab. 35, 1563–1579 (2023).

    Article  CAS  PubMed  Google Scholar 

  122. Yue, Q. et al. Histone H3K9 lactylation confers temozolomide resistance in glioblastoma via LUC7L2-mediated MLH1 intron retention. Adv. Sci. 11, e2309290 (2024).

    Article  Google Scholar 

  123. Yang, L. et al. Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD. J. Hepatol. 81, 651–666 (2024).

    Article  CAS  PubMed  Google Scholar 

  124. Qiao, Z. et al. Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells. Mol. Cell. Biochem. 479, 3063–3076 (2024).

    Article  CAS  PubMed  Google Scholar 

  125. Yu, J. et al. Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 22, 85 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Gu, X. et al. Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. Nucleic Acids Res. 52, 2273–2289 (2024).

    Article  CAS  PubMed  Google Scholar 

  127. Pandkar, M. R., Sinha, S., Samaiya, A. & Shukla, S. Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression. Transl. Oncol. 37, 101758 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Xie, B. et al. CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer. Mol. Cancer 22, 151 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Brand, A. et al. LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK Cells. Cell Metab. 24, 657–671 (2016).

    Article  CAS  PubMed  Google Scholar 

  130. Watson, M. J. et al. Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature 591, 645–651 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Angelin, A. et al. Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments. Cell Metab. 25, 1282–1293 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Gottfried, E. et al. Tumor-derived lactic acid modulates dendritic cell activation and antigen expression. Blood 107, 2013–2021 (2006).

    Article  CAS  PubMed  Google Scholar 

  133. Puig-Kroger, A. et al. Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucose-degradation products. J. Leukoc. Biol. 73, 482–492 (2003).

    Article  CAS  PubMed  Google Scholar 

  134. Colegio, O. R. et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513, 559–563 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Zhou, C. et al. Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death. Nat. Commun. 15, 499 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Gu, J. et al. Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-beta signaling in regulatory T cells. Cell Rep. 40, 111122 (2022).

    Article  CAS  PubMed  Google Scholar 

  137. De Leo, A. et al. Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma. Immunity 57, 1105–1123 (2024).

    Article  PubMed  Google Scholar 

  138. Xiong, J. et al. Lactylation-driven METTL3-mediated RNA m(6)A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol. Cell 82, 1660–1677 (2022).

    Article  CAS  PubMed  Google Scholar 

  139. Weil, M. H. & Afifi, A. A. Experimental and clinical studies on lactate and pyruvate as indicators of the severity of acute circulatory failure (shock). Circulation 41, 989–1001 (1970).

    Article  CAS  PubMed  Google Scholar 

  140. Singer, M. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315, 801–810 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Zhang, T. et al. Lactate’s impact on immune cells in sepsis: unraveling the complex interplay. Front. Immunol. 15, 1483400 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wang, H. C. et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248–251 (1999).

    Article  CAS  PubMed  Google Scholar 

  143. Yang, K. et al. Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis. Cell Death Differ. 29, 133–146 (2022).

    Article  CAS  PubMed  Google Scholar 

  144. Lelubre, C. & Vincent, J. L. Mechanisms and treatment of organ failure in sepsis. Nat. Rev. Nephrol. 14, 417–427 (2018).

    Article  PubMed  Google Scholar 

  145. An, S. et al. PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation. Cell Death Dis. 14, 457 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Wu, D. et al. Histone lactylation-regulated METTL3 promotes ferroptosis via m6A-modification on ACSL4 in sepsis-associated lung injury. Redox. Biol. 74, 103194 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Lood, C. et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat. Med. 22, 146–153 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Caielli, S. et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell 184, 4464–4479 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Zhang, J. et al. Mitochondrial DNA programs lactylation of cGAS to induce IFN responses in patients with systemic lupus erythematosus. J. immunol. 213, 795–807 (2024).

    Article  CAS  PubMed  Google Scholar 

  150. Knochelmann, H. M. et al. When worlds collide: TH17 and Treg cells in cancer and autoimmunity. Cell. Mol. Immunol. 15, 458–469 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Fan, W. et al. Global lactylome reveals lactylation-dependent mechanisms underlying TH17 differentiation in experimental autoimmune uveitis. Sci. Adv. 9, eadh4655 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Pan, R. Y. et al. Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer’s disease. Cell Metab. 34, 634–63 (2022).

    Article  CAS  PubMed  Google Scholar 

  153. Lin, X. et al. Augmentation of scleral glycolysis promotes myopia through histone lactylation. Cell Metab. 36, 511–525 (2024).

    Article  CAS  PubMed  Google Scholar 

  154. Wang, P. et al. H3K18 lactylation promotes the progression of arsenite-related idiopathic pulmonary fibrosis via YTHDF1/m6A/NREP. J. Hazard. Mater. 461, 132582 (2024).

    Article  CAS  PubMed  Google Scholar 

  155. Wang, Y. et al. The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation. Kidney Int. 106, 226–240 (2024).

    Article  CAS  PubMed  Google Scholar 

  156. Rho, H., Terry, A. R., Chronis, C. & Hay, N. Hexokinase 2-mediated gene expression via histone lactylation is required for hepatic stellate cell activation and liver fibrosis. Cell Metab. 35, 1406–1423 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Varner, E. L. et al. Quantification of lactoyl-CoA (lactyl-CoA) by liquid chromatography mass spectrometry in mammalian cells and tissues. Open Biol. 10, 200187 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Li, H., Sun, L., Gao, P. & Hu, H. Lactylation in cancer: current understanding and challenges. Cancer Cell 42, 1803–1807 (2024).

    Article  CAS  PubMed  Google Scholar 

  159. Patel, S. S. & Walt, D. R. Substrate specificity of acetyl coenzyme A synthetase. J. Biol. Chem. 262, 7132–7134 (1987).

    Article  CAS  PubMed  Google Scholar 

  160. Watkins, P. A., Maiguel, D., Jia, Z. & Pevsner, J. Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J. Lipid Res. 48, 2736–2750 (2007).

    Article  CAS  PubMed  Google Scholar 

  161. McElroy, W. D., DeLuca, M. & Travis, J. Molecular uniformity in biological catalyses. The enzymes concerned with firefly luciferin, amino acid, and fatty acid utilization are compared. Science 157, 150–160 (1967).

    Article  CAS  PubMed  Google Scholar 

  162. Gulick, A. M. Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase. ACS Chem. Biol. 4, 811–827 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Schmelz, S. & Naismith, J. H. Adenylate-forming enzymes. Curr. Opin. Struct. Biol. 19, 666–671 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Jakubowski, H. Aminoacylation of coenzyme A and pantetheine by aminoacyl-tRNA synthetases: possible link between noncoded and coded peptide synthesis. Biochemistry 37, 5147–5153 (1998).

    Article  CAS  PubMed  Google Scholar 

  165. Dong, H. et al. YiaC and CobB regulate lysine lactylation in Escherichia coli. Nat. Commun. 13, 6628 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Zhang, X. et al. Screening, expression, purification and characterization of CoA-transferases for lactoyl-CoA generation. J. Ind. Microbiol. Biotechnol. 46, 899–909 (2019).

    Article  CAS  PubMed  Google Scholar 

  167. Li, X. et al. TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation. Eur. Heart J. 45, 4219–4235 (2024).

    Article  CAS  PubMed  Google Scholar 

  168. Xu, X. et al. Sox10 escalates vascular inflammation by mediating vascular smooth muscle cell transdifferentiation and pyroptosis in neointimal hyperplasia. Cell Rep. 42, 112869 (2023).

    Article  CAS  PubMed  Google Scholar 

  169. Dong, M. et al. ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT. Acta Pharm. Sin. B 14, 3027–3048 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Wang, Y. et al. Exercise-induced endothelial Mecp2 lactylation suppresses atherosclerosis via the Ereg/MAPK signalling pathway. Atherosclerosis 375, 45–58 (2023).

    Article  CAS  PubMed  Google Scholar 

  171. Chen, X. et al. High-intensity interval training induces lactylation of fatty acid synthase to inhibit lipid synthesis. BMC Biol. 21, 196 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Ma, W. et al. Orphan nuclear receptor NR4A3 promotes vascular calcification via histone lactylation. Circ. Res. 134, 1427–1447 (2024).

    Article  CAS  PubMed  Google Scholar 

  173. Wang, C. et al. Andrographolide regulates H3 histone lactylation by interfering with p300 to alleviate aortic valve calcification. Br. J. Pharmacol. 181, 1843–1856 (2024).

    Article  CAS  PubMed  Google Scholar 

  174. Chen, B. et al. Metabolic recoding of NSUN2-mediated m5C modification promotes the progression of colorectal cancer via the NSUN2/YBX1/m5C-ENO1 positive feedback loop. Adv. Sci.11, e2309840 (2024).

    Article  Google Scholar 

  175. Wang, J. W. et al. Enterobacterial LPS-inducible LINC00152 is regulated by histone lactylation and promotes cancer cells invasion and migration. Front. Cell. Infect. Microbiol. 12, 913815 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Miao, Z., Zhao, X. & Liu, X. Hypoxia induced beta-catenin lactylation promotes the cell proliferation and stemness of colorectal cancer through the wnt signaling pathway. Exp. Cell. Res. 422, 113439 (2023).

    Article  CAS  PubMed  Google Scholar 

  177. Liao, J. Y. et al. CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1. Int. J. Biol. Sci. 19, 5218–5232 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Li, F. et al. Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer. Drug Resist. Updat. 73, 101059 (2024).

    Article  CAS  PubMed  Google Scholar 

  179. Meng, Q. F. et al. Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression. J. Exp. Clin. Cancer Res. 43, 36 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Qiao, J. et al. Histone H3K18 and Ezrin lactylation promote renal dysfunction in sepsis-associated acute kidney injury. Adv. Sci. 11, e2307216 (2024).

    Article  Google Scholar 

  181. Huang, J. et al. YY1 lactylation aggravates autoimmune uveitis by enhancing microglial functions via inflammatory genes. Adv. Sci. 11, e2308031 (2024).

    Article  Google Scholar 

  182. Wei, L. et al. H3K18 lactylation of senescent microglia potentiates brain aging and Alzheimer’s disease through the NFκB signaling pathway. J. Neuroinflammation 20, 208 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Hay, N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat. Rev. Cancer 16, 635–649 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Martinez-Outschoorn, U. E. et al. Cancer metabolism: a therapeutic perspective. Nat. Rev. Clin. Oncol. 14, 113 (2017).

    Article  PubMed  Google Scholar 

  185. Stine, Z. E., Schug, Z. T., Salvino, J. M. & Dang, C. V. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug Discov. 21, 141–162 (2022).

    Article  CAS  PubMed  Google Scholar 

  186. Lasko, L. M. et al. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage specific tumours. Nature 550, 128–132 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Topper, M. J. et al. The emerging role of epigenetic therapeutics in immuno-oncology. Nat. Rev. Clin. Oncol. 17, 75–90 (2020).

    Article  PubMed  Google Scholar 

  188. Caruso, J. et al. Ergogenic effects of β-alanine and carnosine: proposed future research to quantify their efficacy. Nutrients 4, 585–601 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Zhu, F. Y. et al. Inhibiting bridge integrator 2 phosphorylation leads to improved oocyte quality, ovarian health and fertility in aging and after chemotherapy in mice. Nat. Aging 1, 1010–1023 (2021).

    Article  PubMed  Google Scholar 

  190. Yao, H. et al. Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours. Nat. Biomed. Eng. 3, 306–317 (2019).

    Article  CAS  PubMed  Google Scholar 

  191. Perez-Salvia, M. & Esteller, M. Bromodomain inhibitors and cancer therapy: from structures to applications. Epigenetics 12, 323–339 (2017).

    Article  PubMed  Google Scholar 

  192. Li, X., Liu, S., Li, X. & Li, X. D. YEATS domains as novel epigenetic readers: structures, functions, and inhibitor development. ACS Chem. Biol. 18, 994–1013 (2022).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (32270822), the Peking-Tsinghua Center for Life Science, the State Key Laboratory of Gene Function and Modulation Research, the School of Life Sciences at Peking University, the Qidong-SLS Innovation Fund and the Clinical Medicine Plus X-Young Scholars Project at Peking University (PKU2024LCXQ025), the Fundamental Research Funds for the Central Universities to D.Z. We were grateful to the members of the Zhang lab for their assistance in proofreading the manuscript. We sincerely apologize to researchers whose important contributions could not be cited owing to space limitations. All figures were created using BioRender.com.

Author information

Author notes

  1. Yuwei Tang

    Present address: Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI, USA

Authors and Affiliations

  1. State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking University, Beijing, China

    Haowen Ren, Yuwei Tang & Di Zhang

  2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Di Zhang

Authors
  1. Haowen Ren
    View author publications

    Search author on:PubMed Google Scholar

  2. Yuwei Tang
    View author publications

    Search author on:PubMed Google Scholar

  3. Di Zhang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

H.R. constructed the figures. D.Z. conceived the manuscript and D.Z., H.R. and Y.T. jointly wrote the manuscript.

Corresponding author

Correspondence to Di Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Metabolism thanks Long Zhang and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Yanina-Yasmin Pesch, in collaboration with the Nature Metabolism team.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, H., Tang, Y. & Zhang, D. The emerging role of protein l-lactylation in metabolic regulation and cell signalling. Nat Metab 7, 647–664 (2025). https://doi.org/10.1038/s42255-025-01259-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s42255-025-01259-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing