Fig. 1.

The spatial organization of glucose metabolism machineries across axon. A. Upper panel: Heat map description of the degree of energy consumption by each axonal activity within three axonal subdomains. Bottom panel: the intensity of each feature/parameter of glucose metabolism machineries within three axonal subdomains. Heat map color from white to dark represents the mild to strong degree/intensity. B.-D. The spatial organization of glucose transporters (GLUTs), monocarboxylic acid transporters (MCTs), glycolytic enzymes, mitochondria, and glial partners in axon initial segment (B), myelinated axonal shaft (C), and axonal arbors (D). D. The activity driven adaption of glucose metabolism machineries in presynaptic compartments. ① Activity dependent recruitment and anchoring of mitochondria to F actin filament at presynaptic sites through the AMPK-PAK-Syntaphilin axis; ② Neuronal stimulation induced mitochondrial ultrastructural changes with wider cristae and more compact or irregular matrices; ③ Surface mobilization of GLUT4, and presumably increased glucose uptake and glucose metabolism; and ④ Increased glucose metabolism through the Hexosamine synthesis pathway to boost O-GlcNAcylation of mitochondrial adaptor protein Milton, which reduce mitochondria mobility