FIGURE 1.

Succinate is a signal generated in response to activation of TLR4 by LPS, leading to HIF1α activation. Activation of TLR4 by LPS leads to a profound change in metabolism, including increased glycolysis and the pentose phosphate pathway (not shown). In addition, LPS alters the TCA cycle such that there is an increase in succinate. This occurs via the alteration in glutamine metabolism via both anaplerosis to α-KG and the GABA shunt. Succinate then inhibits PHDs, increasing HIF1α and promoting the expression of IL-1β and other genes. The increase in succinate may also promote protein succinylation, the consequences of which are not yet known.