作为糖酵解的副产物,乳酸长期以来被认为是一种代谢废物。 肿瘤细胞中瓦博格效应的发现使研究人员重新审视 乳酸,并先后阐明乳酸在充当燃料和信号分子、促进血管生成以及抑制肿瘤免疫细胞等方面的关键作用,然而乳酸调控上述 生物学功能的分子机制还不明确。 细胞生命活动产生的数千种代谢小分子不仅仅是蛋白质(酶)催化的产物,同时也能够反 过来通过共价修饰的方式影响蛋白质的功能。 2019 年末和 2020 年初,有两个研究组独立报道了以乳酸为底物的一种新型蛋 白质翻译后修饰———蛋白质乳酸化,并揭示了乳酸化是乳酸对细胞生命活动进行调节的一种重要手段。 本文简要描述了乳 酸化的发现过程,总结了乳酸化的潜在“写入者”和“擦除者”、多种生物体中蛋白质乳酸化图谱概况以及乳酸化在不同生理和 病理过程中调节作用的最新研究进展,并展望了未来蛋白质乳酸化研究的关键问题和科学意义。

Lactate the byproduct of glycolysis has long been considered as a waste metabolite. The discovery of Warburg effect in cancer cells brought our attention back to lactate and inspired us to uncover the crucial roles of lactate in serving as fuel acting as a signal molecule promoting angiogenesis and suppressing immune cells. However the mechanism regarding how lactate regulates these biological processes remains elusive. As we known thousands of metabolites will be produced during life activities. They are not only the products catalyzed by proteins enzymes but also can in turn affect the function of proteins through covalent modification. In 2019 and 2020 lactate was reported to be the substrate of lactylation by two independent studies and this novel post-translational modification revealed another layer of molecular mechanism by which lactate regulates cellular activities. In this review we briefly describe the discovery of lactylation and we summarize the recent advances with respect to the potential 􀆵writer and 􀆵eraser of lactylation the profiling of protein lactylation in a variety of organisms and the regulatory roles of lactylation in diverse physiological and pathological processes. Key questions and potential implications for future studies on lactylation are also discussed.