ArticleThe Journal of biological chemistry2014
Phosphatidylethanolamine synthesis in the parasite mitochondrion is required for efficient growth but dispensable for survival of Toxoplasma gondii.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- An ER-IMC bridge protein TgVPS13A and an IMC-resident scramblase TgDAT1 drive daughter budding in Toxoplasma gondii.PLoS pathogens · 2026Article
- Sarcoendoplasmic reticulum calcium ATPase is an essential and druggable lipid-dependent ion pump in Toxoplasma gondii.Communications biology · 2025Article
- High-density SNP-based linkage map construction and QTL analysis for growth-related traits inFrontiers in genetics · 2025Article
- CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection.Nature microbiology · 2024Article
- Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii.Nature communications · 2024Article
- Lipid metabolism: the potential targets for toxoplasmosis treatment.Parasites & vectors · 2024Review
- Unique asymmetric distribution of phosphatidylserine and phosphatidylethanolamine in Toxoplasma gondii revealed by nanoscale analysis.Histochemistry and cell biology · 2023Article
- Synthesis vs. salvage of ester- and ether-linked phosphatidylethanolamine in the intracellular protozoan pathogen Toxoplasma gondii.Communications biology · 2023Article
- Apically-located P4-ATPase1-Lem1 complex internalizes phosphatidylserine and regulates motility-dependent invasion and egress inComputational and structural biotechnology journal · 2023Article
- Metabolic flexibilities and vulnerabilities in the pentose phosphate pathway of the zoonotic pathogen Toxoplasma gondii.PLoS pathogens · 2022Article
- An essential vesicular-trafficking phospholipase mediates neutral lipid synthesis and contributes to hemozoin formation in Plasmodium falciparum.BMC biology · 2021Article
- Protein kinase TgCDPK7 regulates vesicular trafficking and phospholipid synthesis in Toxoplasma gondii.PLoS pathogens · 2021Article
- Phosphatidylinositol synthesis, its selective salvage, and inter-regulation of anionic phospholipids in Toxoplasma gondii.Communications biology · 2020Article
- High-throughput screening for phosphatidylserine decarboxylase inhibitors using a distyrylbenzene-bis-aldehyde (DSB-3)-based fluorescence assay.The Journal of biological chemistry · 2019Article
- The intracellular parasiteThe Journal of biological chemistry · 2018Article
- Elucidating the mitochondrial proteome ofeLife · 2018Article
- PS, It's Complicated: The Roles of Phosphatidylserine and Phosphatidylethanolamine in the Pathogenesis of Candida albicans and Other Microbial Pathogens.Journal of fungi (Basel, Switzerland) · 2018Review
- A novel fluorescence assay for measuring phosphatidylserine decarboxylase catalysis.The Journal of biological chemistry · 2018Article
- Lipid analysis ofCell discovery · 2018Article
- A CTP Synthase Undergoing Stage-Specific Spatial Expression Is Essential for the Survival of the Intracellular ParasiteFrontiers in cellular and infection microbiology · 2018Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toxoplasma gondii is a highly prevalent obligate intracellular parasite of the phylum Apicomplexa, which also includes other parasites of clinical and/or veterinary importance, such as Plasmodium, Cryptosporidium, and Eimeria. Acute infection by Toxoplasma is hallmarked by rapid proliferation in its host cells and requires a significant synthesis of parasite membranes. Phosphatidylethanolamine (PtdEtn) is the second major phospholipid class in T. gondii. Here, we reveal that PtdEtn is produced in the parasite mitochondrion and parasitophorous vacuole by decarboxylation of phosphatidylserine (PtdSer) and in the endoplasmic reticulum by fusion of CDP-ethanolamine and diacylglycerol. PtdEtn in the mitochondrion is synthesized by a phosphatidylserine decarboxylase (TgPSD1mt) of the type I class. TgPSD1mt harbors a targeting peptide at its N terminus that is required for the mitochondrial localization but not for the catalytic activity. Ablation of TgPSD1mt expression caused up to 45% growth impairment in the parasite mutant. The PtdEtn content of the mutant was unaffected, however, suggesting the presence of compensatory mechanisms. Indeed, metabolic labeling revealed an increased usage of ethanolamine for PtdEtn synthesis by the mutant. Likewise, depletion of nutrients exacerbated the growth defect (∼56%), which was partially restored by ethanolamine. Besides, the survival and residual growth of the TgPSD1mt mutant in the nutrient-depleted medium also indicated additional routes of PtdEtn biogenesis, such as acquisition of host-derived lipid. Collectively, the work demonstrates a metabolic cooperativity between the parasite organelles, which ensures a sustained lipid synthesis, survival and growth of T. gondii in varying nutritional milieus.
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