研究动态
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乳酸和乳酰化:常规碳源和新型修饰在人类疾病中的临床应用。

Lactate and lactylation: Clinical applications of routine carbon source and novel modification in human diseases.

发表日期:2023 Sep 05
作者: Zhimin Wang, Dan Hao, Shuiying Zhao, Ziyin Zhang, Zhen Zeng, Xiao Wang
来源: Epigenetics & Chromatin

摘要:

细胞代谢产生大量的中间代谢产物,这些产物可以作为后翻译修饰的反馈和前馈调节物质。乳酸是糖酵解的代谢产物,最近被认为通过代谢重组和表观遗传修饰,在细胞特性塑造中发挥了多效作用。来自葡萄糖的乳酸来源碳在糖酵解、乳酸和乳酰化之间介导了相互交流。此外,乳酸的多种代谢命运使其成为临床应用中理想的代谢成像底物。多项研究已经确定了蛋白质乳酰化在与细胞命运决定、胚胎发育、炎症、肿瘤和神经精神障碍相关的人类疾病中的关键作用。在本综述中,我们将重点讨论乳酸来源碳的代谢命运,为进一步研究和治疗人类疾病提供有用信息。我们全面讨论了在糖酵解调控过程中的重编程和修饰作用、超极化乳酸信号的临床转化前景、人类疾病中的乳酰修饰,以及与其他技术和组学的应用。版权所有© 2023作者。由Elsevier公司出版。保留所有权利。
Cell metabolism generates numerous intermediate metabolites that could serve as feedback and feed-forward regulation substances for post-translational modification. Lactate, a metabolic product of glycolysis, has recently been conceptualized to play a pleiotropic role in shaping cell identities through metabolic rewiring and epigenetic modifications. Lactate-derived carbons, sourced from glucose, mediate the crosstalk among glycolysis, lactate and lactylation. Furthermore, the multiple metabolic fates of lactate make it an ideal substrate for metabolic imaging in clinical application. Several studies have identified the crucial role of protein lactylation in human diseases associated with cell fate determination, embryonic development, inflammation, neoplasm and neuropsychiatric disorders. Herein, this review will focus on the metabolic fate of lactate-derived carbon to provide useful information for further research and therapeutic approaches in human diseases. We comprehensively discuss its role in reprogramming and modification during the regulation of glycolysis, the clinical translation prospects of the hyperpolarized lactate signal, lactyl modification in human diseases, and its application with other techniques and omics.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.