Fig. 2
From: Axonal energy metabolism, and the effects in aging and neurodegenerative diseases
The molecular underpinnings of NAD redox potential maintenance in axons. A. A schematic view of NAD biosynthetic pathways. B. Heat map visualization of the abundance of mRNA and proteins of NAD biosynthetic enzymes. Transcript levels are adapted from [259]; protein levels are adapted from [260]. Abbreviations: Inh. Neu, inhibitory neurons; Exc. Neu, excitatory neurons; Mic. Mac., microglia and macrophages; Oligo, oligodendrocytes; OPC, oligodendrocyte precursor cells; Fibro.-like, fibroblast-like cells; End, endothelial cells. C. The subcellular localization of NMNAT1-3 in the soma and proximal axon. D. The subcellular distribution of NMNAT2, NMNAT3, and proteins involved in NAD+/NADH homeostasis in presynaptic boutons. (D1) NMNAT2, LDH-A, and glycolytic enzymes closely attach to synaptic vesicles; NMNAT2 inhibits SARM1 activation and maintains local NAD redox potential together with LDH-A to support “onboard” glycolysis; (D2) NMNAT3 inside mitochondrial matrix maintains local NAD redox potential together with OXPHO units, SLC25A51 (NAD+ transporter), and Malate-Aspartate shuttle. E. A hypothetical model of mitochondrial independent NAD+ recycling through the glutamine carboxylation pathway. MDH1, cytosolic malate dehydrogenase 1; ACLY, ATP citrate lyase; GLS, glutaminase; Gln, glutamine; Glu, glutamate; GOT1, glutamic-oxaloacetic transaminase 1; α-KG, alpha ketoglutarate; IDH1, isocitrate dehydrogenase (NADP+) 1; OAA, oxaloacetate