Xuechao Fei, Ming Zhao, Lingling Zhu
Lactate is a product of cellular energy metabolism. In the brain, lactate shuttles between astrocytes, microglia, and neurons, playing an important role in coordinating cellular metabolism and signaling. Hypoxia causes a shift in cellular metabolism from oxidative phosphorylation to glycolysis, increasing lactate. In addition to being a metabolic substrate, lactate also acts as a signaling molecule. More interestingly, lactate accumulation can induce protein lactylation modification, a newly identified post-translational modification (PTM). Lactylation modifications occur on both histone and non-histone proteins and are involved in the regulation of numerous cellular processes, including tumorigenesis, immune inflammation, and embryonic development. In the context of neuroinflammation, our recently published report showed that hypoxia activates microglia and exacerbates neuroinflammation in the brain. This review summarizes the effects of hypoxia on lactate metabolism, as well as the process of lactylation and delactylation in microglia. The regulatory mechanisms of protein lactylation in hypoxia-exacerbated neuroinflammation are further discussed.
