H4K8 lactylation of MFN2 mediating mitochondrial transfer and aerobic glycolytic pathway in the pathogenesis of glaucoma

Under high intraocular pressure conditions, retinas undergo a marked enhancement of glycolytic activity, leading to the production of large quantities of lactate to fulfill the energy requirements of neurons leading to the production of large quantities of lactate to fulfill the energy requirements of neurons. Here, we show muller cells activation may cause mitochondria morphology synchronous changes both in retinal ganglion cells RGCs and photoreceptor cells in glaucoma animal model. After detecting elevated histone lactylation in retinas from high intraocular pressure model mice, we observed that histone H4 lysine 8 lactylation H4K8la levels are elevated obviously; using cleavage under targets and tagmentation CUT Tag technique, we found that H4K8la is enriched on the promoter of MFN2, which modified by the lactate-dependent histone.