Fig. 1: Regulation of cGAS activity and innate immunity by AARS2-mediated lactylation.
From: Encoding immune responses: the moonlighting function of alanyl-tRNA synthetase
In hyperlactatemia (H-Lac), lactic acidosis (LA), and anxiety patients, excess L-lactates are transported into the cytoplasm by MCT1. Then AARS2 senses L-lactate and mediates the lactylation of cGAS proteins. The lactylation reverses cGAS function from sensing DNA to repelling DNA, resulting in the attenuation of cGAMP production and downstream innate immune responses.
