The figure illustrates the key pathways involved in lactate signaling, including glycolysis, lactylation, lactate transport via monocarboxylate transporters (MCTs and SMCTs), and lactate-mediated activation of G-protein-coupled receptors (GPR81 and GPR132). Glycolysis produces lactate through LDH-mediated conversion of pyruvate, and lactate can be exported out of the cell via MCT4 or imported into cells via MCT1 and SMCTs. Inside the cell, lactate can undergo lactylation, a post-translational modification affecting histones (and cytoplasmic proteins) and modulating gene expression. Extracellular lactate binds to GPR receptors, such as GPR81, initiating downstream signaling cascades that influence immune and endothelial cell functions. The figure also highlights potential drugs currently under investigation to target these pathways. These therapeutic strategies are being explored to modulate the impact of lactate in diseases like cancer and inflammation.
