Fig. 5
ATP-producing metabolic pathways in distinct immune cell subsets. Glucose oxidation to pyruvate via glycolysis is a fast reaction generating 2 mol of ATP per mol glucose. This aerobic glycolysis is complemented by the PPP that can produce further metabolic precursor molecules and is involved in ROS production. Pyruvate can be converted to lactate or further oxidized to acetyl-CoA entering the mitochondrial TCA cycle (yellow box). The TCA cycle (red box) generates reducing equivalents NADH and FADH2 which are utilized in the mitochondrial respiratory chain to build up the proton gradient across the mitochondrial inner membrane by complexes I–IV of the respiratory chain. As a by-product, ROS and RNS are produced. OXPHOS produces larger amounts of ATP (~ 30 mol/mol glucose) by complex V. Immune cells are also able to utilize substrates such as glutamine, which enters these pathways via the TCA metabolite α-ketoglutarate and FA, which are oxidized to acetyl-CoA via β-oxidation. Granulocytes and M1 macrophages (yellow box) have a highly glycolytic metabolism even when O2 is available. Their TCA cycle and respiratory chain activity are maintained at a low level. Tn, Tm, and Treg cells, as well as monocytes and M2 macrophages, primarily perform OXPHOS and are also able to metabolize FA and glutamine in order to fuel the TCA cycle (red box). Teff cells (green box) have a highly active metabolism including all of the pathways described. ADP adenosine diphosphate, ATP adenosine triphosphate, CoA coenzyme A, FADH2/FAD flavin adenine dinucleotide in its reduced/oxidized form, H2O water, IMS intermembrane space, MM mitochondrial membrane, NADH/NAD+ nicotinamide adenine dinucleotide in its reduced/oxidized form, O2 oxygen, OXPHOS oxidative phosphorylation, PPP pentose phosphate pathway, ROS reactive O2 species, RNS reactive nitrogen species, TCA tricarboxylic acid cycle, Teff effector T cell, Tn naïve T cell, Tm memory T cell, Treg regulatory T cell. Reprinted with permission from Zhang et al. 2020 [105]