Figure 5.

The Metabolic Signature of Autoreactive T cells in Rheumatoid Arthritis. Schematic diagram of metabolic pathways in health and RA T cells. Healthy T cell: Low-proliferating healthy T cells (naïve, memory) rely on mitochondrial energy production. When differentiating into highly replicating effector T cells, bioenergetic and biosynthetic needs are fulfilled by engaging glycolysis. RA T cells: Biased toward biomass generation, RA T cells shunt glucose into the pentose phosphate pathway and produce NADPH. Mitochondria with unrepaired mtDNA utilize relatively low amounts of oxygen and produce low concentrations of ROS. Mitochondrial succinate production is suppressed due to low activity of Succinate-CoA ligase and a-ketoglutarate is converted into citrate. Exported citrate supplies cytoplasmic acetyl-CoA pools and promotes lipogenesis. Surplus lipids sustain the generation of invasive membrane ruffles and of cellular uropods. With low ATP production, RA T cells require external energy sources, such as glutamine and lactate to meet basic bioenergetic needs. By diverting energy away from ATP production toward assembly of biosynthetic precursor molecules, RA T nourish the emergence and the survival of replicating effector T cells that are tissue-invasive and pro-inflammatory. α-KG, α-ketoglutarate; mtDNA, mitochondrial DNA.