Cell-free synthesis, reconstitution, and characterization of a mitochondrial dicarboxylate-tricarboxylate carrier of Plasmodium falciparum.

The malaria parasite, Plasmodium falciparum, was recently shown to operate a branched pathway of tricarboxylic acid (TCA) metabolism. To identify and characterize membrane transporters required for such TCA metabolism in the parasite, we isolated a cDNA for a dicarboxylate-tricarboxylate carrier homolog (PfDTC), synthesized the encoded protein with the use of a cell-free translation system, and determined the substrate specificity of its transport activity with a proteoliposome reconstitution system. PfDTC was found to mediate efficient oxoglutarate-malate, oxoglutarate-oxaloacetate, or oxoglutarate-oxoglutarate exchange across the liposome membrane. Our results suggest that PfDTC may mediate the oxoglutarate-malate exchange across the inner mitochondrial membrane required for the branched pathway of TCA metabolism in the malaria parasite.