乳酰化：心肌缺血‒再灌注损伤中的代谢表观遗传调控与细胞死亡机制
Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.
摘要(中文译文)
心肌梗死(myocardial infarction, MI)血运重建后导致后续损伤的一个重要致病过程是心肌缺血/再灌注损伤(myocardial ischemia/reperfusion injury, MI/RI)。其潜在机制受乙酰化、甲基化、磷酸化和泛素化等传统翻译后修饰(post-translational modifications, PTMs)调控，并涉及自噬、凋亡、焦亡和铁死亡等多种细胞死亡途径。组蛋白赖氨酸乳酰化(histone lysine lactylation, Kla)作为一种新型的代谢相关表观遗传调控机制，近年来备受关注。本综述系统阐明了乳酸在心脏能量代谢中的关键作用及其对Kla修饰的影响，探讨了Kla在MI/RI中的双重调控功能。研究显示，Kla与乙酰化、磷酸化、N6-甲基腺苷(N6-methyladenosine, m6A)甲基化及泛素化等变化之间存在显著的相互作用，从而建立了调控MI/RI中细胞死亡的推定联系。靶向乳酸脱氢酶A(lactate dehydrogenase A, LDHA)、单羧酸转运蛋白(monocarboxylate transporters, MCTs)和组蛋白去乙酰化酶(histone deacetylases, HDACs)等乳酸相关分子显示出治疗潜力。因此，本文探讨了可应用于MI/RI不同阶段的靶向干预分子。最终，阐明Kla的动态变化模式及其在各种生物学过程中的关键参与，将为MI/RI的预防和治疗创造新范式并提供潜在治疗靶点。
Abstract
One important pathogenic process that contributes to subsequent damage after myocardial infarction (MI) revascularization is myocardial ischemia/reperfusion injury (MI/RI). Its underlying mechanisms are controlled by traditional post-translational modifications (PTMs) like acetylation, methylation, phosphorylation, and ubiquitination, and involve several cell death pathways, such as autophagy, apoptosis, pyroptosis, and ferroptosis. Histone lysine lactylation (Kla), a novel metabolically related epigenetic regulation mechanism, has attracted a lot of attention in recent years. This review systematically clarifies the crucial role of lactate in cardiac energy metabolism and its influence on Kla modification, exploring Kla's dual regulatory function in MI/RI. It demonstrates a significant interaction between Kla and changes like acetylation, phosphorylation, N6-methyladenosine (m6A) methylation, and ubiquitination, thereby establishing putative connections that regulate cell death in MI/RI. Targeting lactate-related molecules such as lactate dehydrogenase A (LDHA), monocarboxylate transporters (MCTs), and histone deacetylases (HDACs) shows therapeutic potential. Therefore, targeted intervention molecules applicable at different stages of MI/RI are explored. Ultimately, elucidating the dynamic patterns of Kla and its crucial involvement in various biological processes will create new paradigms and potential therapeutic targets for the prevention and treatment of MI/RI.
如何引用
AMA
Xiaoting Yang, Hui Wu, Di Liu, Gang Zhou, Dong Zhang, Yanfang Liu, et al. Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.. Genes & diseases. 2027; doi:10.1016/j.gendis.2026.102211.
APA
Xiaoting Yang, Hui Wu, Di Liu, Gang Zhou, Dong Zhang, Yanfang Liu, et al (2027). Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.. Genes & diseases. https://doi.org/10.1016/j.gendis.2026.102211
GB/T 7714
Xiaoting Yang, Hui Wu, Di Liu, Gang Zhou, Dong Zhang, Yanfang Liu, et al. Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.[J]. Genes & diseases, 2027 doi:10.1016/j.gendis.2026.102211.
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