Figure 9.

A prototype model featuring the function of TgPEPCK_mt as a metabolic shunt in central carbon metabolism of tachyzoites. Schemes are constructed based on this study and earlier work. In cells with an intact glycolysis (left), the mitochondrial PEPCK maintains a homeostatic bidirectional flow of glucose and glutamine-derived carbon, which may enable integrated use of both nutrients and rapid metabolic rewiring in response to nutritional oscillations within and/or outside host cells. Neither glucose nor glutamine alone produces significant amounts of fully labeled citrate, suggesting co-usage of both nutrients to operate the TCA cycle (depicted by green/red colors). A minor amount of (+6)-citrate that is produced from glucose requires a pool of sugar-derived oxaloacetate probably generated by TgPEPCK_mt, because TgPyC and TgPEPCK_net are not expressed and expendable during the lytic cycle. On the other hand, in glycolysis-impaired cells (right), TgPEPCK_mt allows glutamine-fueled gluconeogenic flux to ensure the biosynthetic activities and thereby parasite survival. Likewise, TgPEPCK_mt-derived PEP and ensuing recycling of pyruvate can sustain a glutamine-fueled TCA cycle that is critical to produce energy and reducing equivalents. The work also implicates the presence of a PEP transporter in the membrane of the mitochondrion.