1. Division and Adaptation to Host Environment of Apicomplexan Parasites Depend on Apicoplast Lipid Metabolic Plasticity and Host Organelle Remodeling.
- Author
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Amiar S, Katris NJ, Berry L, Dass S, Duley S, Arnold CS, Shears MJ, Brunet C, Touquet B, McFadden GI, Yamaryo-Botté Y, and Botté CY
- Subjects
- Acyltransferases metabolism, Animals, Cell Membrane metabolism, Cytokinesis, Fatty Acid Synthases metabolism, Fatty Acids biosynthesis, Gene Deletion, Humans, Intracellular Space parasitology, Life Cycle Stages, Lipidomics, Male, Models, Biological, Multivesicular Bodies metabolism, Multivesicular Bodies ultrastructure, Mutation genetics, Nutrients, Parasites growth & development, Parasites physiology, Parasites ultrastructure, Protozoan Proteins metabolism, Toxoplasma growth & development, Toxoplasma ultrastructure, Adaptation, Physiological, Apicoplasts metabolism, Cell Division, Host-Parasite Interactions, Lipid Metabolism, Parasites metabolism, Toxoplasma metabolism, Toxoplasma physiology
- Abstract
Apicomplexan parasites are unicellular eukaryotic pathogens that must obtain and combine lipids from both host cell scavenging and de novo synthesis to maintain parasite propagation and survival within their human host. Major questions on the role and regulation of each lipid source upon fluctuating host nutritional conditions remain unanswered. Characterization of an apicoplast acyltransferase, TgATS2, shows that the apicoplast provides (lyso)phosphatidic acid, required for the recruitment of a critical dynamin (TgDrpC) during parasite cytokinesis. Disruption of TgATS2 also leads parasites to shift metabolic lipid acquisition from de novo synthesis toward host scavenging. We show that both lipid scavenging and de novo synthesis pathways in wild-type parasites exhibit major metabolic and cellular plasticity upon sensing host lipid-deprived environments through concomitant (1) upregulation of de novo fatty acid synthesis capacities in the apicoplast and (2) parasite-driven host remodeling to generate multi-membrane-bound structures from host organelles that are imported toward the parasite., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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