PFKM通过经典与非经典途径调控巨噬细胞功能的研究进展OA

Phosphofructokinase,muscle type(PFKM)is a key rate-limiting enzyme in the glycolytic pathway,and its expression and activity are regulated by multiple signaling pathways,including hypoxia-inducible factor-1 alpha(HIF-1α),myelocytomatosis oncogene(Myc),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),and adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK).Recent studies have demonstrated that PFKM reprograms macrophage functions through both the canonical glycolytic pathway and"non-canonical"functions.Physicochemical factors in the microenvironment,including mechanical forces,glucose,and citrate,can shift the equilibrium between the tetrameric and dimeric conformations of PFKM,thereby facilitating the switch between its classical and non-classical functions.While current research has largely focused on the classical glycolytic role of PFKM,its non-canonical functions and the underlying molecular mechanisms remain to be fully elucidated.This review summarizes the classical and non-canonical roles of PFKM in macrophages,its upstream regulatory signals,and its implications in infectious diseases and cancer,aiming to provide a theoretical foundation and insights for PFKM-targeted immunometabolic therapeutic strategies.