蛋白质乳酸化修饰调控疾病发生的研究进展

Advances in regulation of disease development by protein lactylation modifications

细胞内的乳酸主要来源于糖酵解过程,作为葡萄糖代谢的经典副产物,很长一段时间被误认为是代谢废物[1]。在缺氧条件下,葡萄糖进入细胞质后经过一系列催化反应转化为丙酮酸,因为缺氧抑制三羧酸循环,丙酮酸不进入线粒体进行氧化,糖酵解途径被激活,丙酮酸在乳酸脱氢酶的作用下直接还原为乳酸[2]。乳酸作为细胞糖酵解途径重要的含碳代谢产物,因肿瘤细胞中沃伯格(Warburg)效应的存在,最近它的生物学功能重新得到了人们的广泛关注并开始对其调控机制进行了更深入的探索与研究[3-4]。

Known as a classic product of glucose metabolism,lactic acid has been regarded as a metabolic waste.However,it wasn't until the discovery of Warburg effect in tumors that researchers refocused on the role of lactic acid in cells.Being a kind of signaling molecule with multiple functions,lactic acid is a key metabolic product connecting glycolysis and oxidative phosphorylation,and it also has non-metabolic activity.Recent studies have shown that lactic acid can be used as a substrate to participate in a novel post-translational modification of proteins,known as protein lactylation.It can be involved in many kinds of diseases,and plays an important role in immune regulation and homeostasis maintenance.This paper briefly describes and summarizes the important role of lactylation modification in the developmental mechanisms of diseases such as tumors,inflammation,neuropsychiatric diseases,cardiocerebrovascular diseases,and so on.