Abstract
Given its various roles in cellular functions, lactate is no longer considered a waste product of metabolism and lactate sensing is a pivotal step in the transduction of lactate signals. Lysine lactylation is a recently identified post-translational modification that serves as an intracellular mechanism of lactate sensing and transfer. Although acetyltransferases such as p300 exhibit general acyl transfer activity, no bona fide lactyltransferases have been identified. Recently, the protein synthesis machinery, alanyl-tRNA synthetase 1 (AARS1), AARS2 and their Escherichia coli orthologue AlaRS, have been shown to be able to sense lactate and mediate lactyl transfer and are thus considered pan-lactyltransferases. Here we highlight the mechanisms and functions of these lactyltransferases and discuss potential strategies that could be exploited for the treatment of human diseases.
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Acknowledgements
The current work was supported by the Chinese National Natural Science Fund (31925013, 32125016, T2321005, U20A20393, 32070907, 31871405, 31870902, W2411011 and U24A20371), a special program of the Ministry of Science and Technology of China (2024YFC2707400, 2021YFA1101000, 2022YFA1105200 and 2023YFA1800200), a Key Research and Development Program of Zhejiang Province (2024C03142), a joint project of the Pinnacle Disciplinary Group, the Second Affiliated Hospital of Chongqing Medical University, the Science Foundation of Jiangsu Province (19KJA550003), the Suzhou Innovation and Entrepreneurship Leading Talent Program (ZXL2022505), a Suzhou Medical College Basic Frontier Innovation cross-research project (YXY2303027), key cross-research projects of the School of Medicine at Soochow University (YXY2303027) and the Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases. We apologize to those researchers whose related work we were not able to cite in this Perspective. Figures were created using BioRender.com.
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Zong, Z., Ren, J., Yang, B. et al. Emerging roles of lysine lactyltransferases and lactylation. Nat Cell Biol 27, 563–574 (2025). https://doi.org/10.1038/s41556-025-01635-8
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DOI: https://doi.org/10.1038/s41556-025-01635-8
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