Article Figures & Data
Figures
- FIGURE 1.
Metabolic shifts in glucose metabolism during an immune response. (A) Naive T cells predominantly use glucose via OxPhos, whereas effector T cells exhibit high glycolytic metabolism. Precursors of aerobic glycolysis fuel biosynthetic pathways in activated cells required for protein and membrane synthesis. (B) Increased PI3K-mTOR signaling, nutrient uptake, and glycolysis are signature features of metabolically activated effector T cells. Memory T cells revert to low nutrient uptake, but are metabolically primed to respond rapidly to inflammatory growth signals or to Ag re-exposure.
- FIGURE 2.
HIV-associated metabolic dysregulation influences immune cell responses, HIV biogenesis, and cell survival. Increased cell surface expression of Glut1 on CD4+ T cells and macrophages enhances glucose uptake. Upregulation of hexokinase (HX) converts glucose into G6P and forward feed to produce phosphoenolpyruvate (PEP), which is converted into pyruvate by pyruvate kinase muscle type 2 (PKM2). Nuclear translocation of PKM2 can induce activation of HIV LTR. Conversely, HX can bind to the outer mitochondrial membrane to maintain mitochondrial membrane potential and confer an antiapoptotic phenotype of macrophages. Increased glycolysis disengages GAPDH from its regulatory control (“moonlighting”) on inflammatory cytokines. Elevated aerobic glycolysis fuels the pentose-phosphate pathway (PPP) to synthesize amino acids and ribose-5-phosphate required for HIV protein and nucleotide synthesis. Upregulation of these metabolic pathways deprives the tricarboxylic cycle precursors for OxPhos, causing decreased mitochondrial ATP production and apoptosis in some effector CD4+ T cells. HIV infection may dysregulate mitochondrial biogenesis, resulting in oxidative stress.
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