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Mitochondrial Metabolism of Glucose and Glutamine Is Required for Intracellular Growth of Toxoplasma gondii


MacRae, JI; Sheiner, L; Nahid, A; Tonkin, C; Striepen, B; McConville, MJ
2012-11-15
CELL HOST & MICROBE
Journal Article
12
5
682-692
Toxoplasma gondii proliferates within host cell vacuoles where the parasite relies on host carbon and nutrients for replication. To assess how T. gondii utilizes these resources, we mapped the carbon metabolism pathways in intracellular and egressed parasite stages. We determined that intracellular T. gondii stages actively catabolize host glucose via a canonical, oxidative tricarboxylic acid (TCA) cycle, a mitochondrial pathway in which organic molecules are broken down to generate energy. These stages also catabolize glutamine via the TCA cycle and an unanticipated gamma-aminobutyric acid (GABA) shunt, which generates GABA and additional molecules that enter the TCA cycle. Chemically inhibiting the TCA cycle completely prevents intracellular parasite replication. Parasites lacking the GABA shunt exhibit attenuated growth and are unable to sustain motility under nutrient-limited conditions, suggesting that GABA functions as a short-term energy reserve. Thus, T. gondii tachyzoites have metabolic flexibility that likely allows the parasite to infect diverse cell types.
CELL PRESS
APICOMPLEXAN PARASITES; DEHYDROGENASE COMPLEX; ACID-METABOLISM; APICOPLAST; TACHYZOITES; INVASION; BEHAVIOR; ENERGY; CYCLE; LOCALIZATION
Infection and Immunity
10.1016/j.chom.2012.09.013
Copyright © 2012 Elsevier Inc. All rights reserved.

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Creation Date 2012-11-15 12:00:00