Lactate Signal: Modulator of Cellular Energy Production and Anabolism.

Lactate is no longer viewed simply as a glycolytic end-product, but as a compartmentalized signaling metabolite that coordinates energy production, carbon redistribution, redox balance, and anabolic commitment. This review discusses lactate as a regulator of the catabolism-anabolism axis, emphasizing two major patterns of molecular interpretation. First, lactate acts through non-covalent mechanisms, including transporter-mediated flux, receptor-dependent sensing, pH-linked effects, and direct binding to intracellular proteins. These processes allow lactate-rich states to rapidly couple metabolic flux to signaling pathways. Second, lactate-associated metabolic states are translated into the dynamic and reversible change of covalent post-translational modifications, including histone and non-histone lactylation. Histone lactylation connects glycolytic metabolism to transcriptional regulation, whereas non-histone lactylation expands lactate-dependent control to immune signaling, mitochondrial metabolism, DNA repair, cardiovascular stress, tissue remodeling, and cancer progression. We further discuss how extracellular, cytosolic, mitochondrial-associated, and nuclear lactate pools provide distinct biochemical contexts in which lactate-dependent mechanisms can operate. By integrating lactate transport, receptor sensing, protein binding, metabolism, and lactylation, this Review uses compartmental organization as a framework for synthesizing how lactate-rich states influence metabolic adaptation, stress responses, immune regulation, tissue remodeling, disease progression, and, in selected contexts, anabolic or reparative programs.