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Tweaking T Cell Bioenergetics

The functional status of lymphocytes is tightly linked to metabolism as glycolysis and mitochondrial respiration supply lymphocyte activation with necessary intermediates. It is currently accepted that resting lymphocytes such as naïve or memory T cells utilize oxidative phosphorylation for ATP production. Following activation, metabolism in T cells switches from catabolic to aerobic anabolic glycolysis and glutaminolysis. This transition is similar to metabolic shift in tumor cells, described as the Warburg effect [1,2]. In Warburgshifted activated T cells, glucose transport is upregulated leading to an overall rise in intracellular glucose levels that result in high production of pyruvate. Further, pyruvate is converted into lactate and secreted out of cells. Also, glycolytic reactions are involved in multiple metabolic pathways, such as pentose phosphate, responsible for synthesis of nucleotides and lipids necessary for the generation of daughter cells during cell divisions. At the same time, Fatty Acid β-Oxidation (FAO), catabolic metabolism of fatty acids, is down-modulated in activated T cells...read more

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