Fig. 10: Mito-nuclear carbon metabolism in Toxoplasma.
Toxoplasma actively catabolizes host glucose via a canonical TCA cycle and also catabolizes glutamine via the GABA shunt and TCA cycle. Mitochondrial-localized MDH-FAD may participate in the TCA cycle, whereas cytoplasmic-localized MDH mediates the interconversion of oxaloacetate and malate. Malate is utilized by ME in the nucleus to produce pyruvate, a step that is essential for the growth and survival of Toxoplasma. The question mark denotes the to-be-identified transporters in the mitochondrion, apicoplast or plasma membranes. Glc glucose, GT1 glucose transporter, PEP phosphoenolpyruvate, Pyr pyruvate, PYK1 pyruvate kinase 1, PYK2 pyruvate kinase 2, APT apicoplast phosphate translocator, APC apicoplast pyruvate carrier, MEP methylerythritol 4-phosphate pathway, FAS II type II fatty acid synthesis pathway, MPC mitochondrial pyruvate carrier, BCKDH branched-chain Ī±-ketoacid dehydrogenase, PyC pyruvate carboxylase, Ac-CoA acetyl-CoA, Cit citrate, iCit isocitrate, Ī±-KG Ī±-ketoglutarate, CS1 citrate synthase 1, CS2 citrate synthase 2, PrpC 2-methylcitrate synthase, ACO aconitase, Iso isocitric acid, IDH1 isocitrate dehydrogenase 1, IDH2 isocitrate dehydrogenase 2, KDH Ī±-ketoglutarate dehydrogenase, SCS succinyl-CoA synthetase, SSADH succinic semialdehyde dehydrogenase, Suc succinate, Fum fumarate, SDH succinate dehydrogenase, FH fumarase, Mal malate, MDH-FAD FAD malate-dehydrogenase, MDH malate dehydrogenase, Oxa oxaloacetate, ME malic enzyme, PEPCK phosphoenolpyruvate carboxykinase, AST aspartate aminotransferase, Asp aspartate, Gln glutamine, Glu glutamate, GluS glutaminase, GDH glutamate dehydrogenase, GAD glutamate decarboxylase, GABA Ī³-aminobutyric acid, GABA-AT gamma-aminobutyric acid-aminotransferase, SSA succinic semialdehyde, SP sodium propionate, Ac acetate, ACS Acetyl-CoA synthetase, NADH nicotinamide adenine dinucleotide, NADPH nicotinamide adenine dinucleotide phosphate, ETC electron transport chain, ATP adenosine triphosphate, AAC1 mitochondrial ADP/ATP Carrier 1, TCA cycle tricarboxylic acid cycle.
