The Mitochondrial Pyruvate Carrier Coupling Glycolysis and the Tricarboxylic Acid Cycle Is Required for the Asexual Reproduction of Toxoplasma gondii
Congcong Lyu, Yukun Chen, Yanan Meng, Jichao Yang, Shu Ye, Zhipeng Niu, Issam EI-Debs, Nishith Gupta, Bang Shen
Abstract
can utilize different carbon sources, pyruvate homeostasis is critical for parasite growth. Pyruvate is produced primarily in the cytosol but metabolized in other organelles, such as the mitochondrion and apicoplast. The mechanism of import and physiological significance of pyruvate in these organelles remains unclear. Here, we identified the transporter of cytosol-derived pyruvate into the mitochondrion and studied its constituent subunits and their relevance. Our results show that cytosolic pyruvate is a major source of acetyl-CoA in the mitochondrion and that the mitochondrial pyruvate transporter is needed for optimal parasite growth. The mutants lacking the transporter are viable and virulent in a mouse model, underscoring the metabolic plasticity in the parasite's mitochondrion.