Fig. 2

Nutrient transport supports NK cell signalling and metabolism. Numerous nutrient transporters that are important for NK cell metabolism have been identified. Slc2a1 and Slc2a3 (also called Glut1 and Glut3) are the major glucose transporters on NK cells. Glucose supports energy production and pathways for biosynthesis and maintaining redox balance in NK cells. The metabolic regulators mTORC1 and cMyc are sensitive to levels of glucose and can be inactive when NK cells are starved of glucose. The amino acid transporter Slc1a5 (glutamine uptake) and Slc7a5 (large neutral amino acid uptake) are also important for sustaining cMyc and mTORC1 signalling, energy production and biosynthesis. The transferrin receptor CD71 is a cMyc target gene and mediates the uptake of iron that is used as a cofactor for diverse enzymes, notably the complexes of the electron transport chain in the mitochondria. Under certain circumstances scavenging receptors for the uptake of lipids and cholesterol can be expressed on NK cells, including CD36 and Scarb1. Fatty acids can act as agonists for PPAR nuclear receptors and this has been linked to metabolic dysfunction, including decreased mitochondrial fitness, in obesity. Cholesterol and oxidised cholesterol molecules such as 25-hydroxycholesterol inhibit SREBP activation causing profound metabolic and functional abnormalities