ArticleProceedings of the National Academy of Sciences of the United States of America2006
Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 257 citations in OpenAlex.
- Article
- Inhibitors of the FASII Metabolic Pathway inMicroorganisms · 2026Review
- Acyl Carrier Protein is Essential for Apicoplast Biogenesis in Malaria Parasites Independent of Fatty Acid Synthesis.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide transcriptomic analysis of Toxoplasma gondii reveals stage-specific regulatory programs and metabolic adaptations driving oocyst sporulation.BMC genomics · 2026Article
- The cell cycle-regulated cytoplasmic kinase, TgCRCK1, is required for efficient propagation of human protozoan pathogen,Microbiology spectrum · 2026Article
- An apicoplast-localized GTPase is essential formSphere · 2026Article
- Transporters, an important but poorly studied area of Toxoplasma gondii.Parasites & vectors · 2026Review
- Transfection of the free-living alga Chromera velia enables direct comparisons with its parasitic apicomplexan relative, Toxoplasma gondii.Journal of cell science · 2026Article
- TgAP2X-7 is a novel cell cycle-regulated transcription factor that plays an essential role inmSphere · 2025Article
- Transfection of the free-living algabioRxiv : the preprint server for biology · 2025Article
- A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma.Nature communications · 2025Article
- TgGloL is an atypical glyoxalase/VOC domain-containing apicoplast protein that is important for the growth ofMolecular biology of the cell · 2025Article
- Mitochondria of a human skeletal muscle cell line associate with the parasitophorous vacuoles of three archetypal lineages ofFEMS microbes · 2025Article
- An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis inOpen biology · 2024Article
- The Toxoplasma gondii F-Box Protein L2 Functions as a Repressor of Stage Specific Gene Expression.PLoS pathogens · 2024Article
- The acyl-CoA synthetasemBio · 2024Article
- Lipid metabolism: the potential targets for toxoplasmosis treatment.Parasites & vectors · 2024Review
- An apicoplast-localized deubiquitinase contributes to the cell growth and apicoplast homeostasis of Toxoplasma gondii.Veterinary research · 2024Article
- Functional screening revealsmBio · 2023Article
- TgKDAC4: A Unique Deacetylase ofMicroorganisms · 2023Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Apicomplexan parasites are the cause of numerous important human diseases including malaria and AIDS-associated opportunistic infections. Drug treatment for these diseases is not satisfactory and is threatened by resistance. The discovery of the apicoplast, a chloroplast-like organelle, presents drug targets unique to these parasites. The apicoplast-localized fatty acid synthesis (FAS II) pathway, a metabolic process fundamentally divergent from the analogous FAS I pathway in humans, represents one such target. However, the specific biological roles of apicoplast FAS II remain elusive. Furthermore, the parasite genome encodes additional and potentially redundant pathways for the synthesis of fatty acids. We have constructed a conditional null mutant of acyl carrier protein, a central component of the FAS II pathway in Toxoplasma gondii. Loss of FAS II severely compromises parasite growth in culture. We show FAS II to be required for the activation of pyruvate dehydrogenase, an important source of the metabolic precursor acetyl-CoA. Interestingly, acyl carrier protein knockout also leads to defects in apicoplast biogenesis and a consequent loss of the organelle. Most importantly, in vivo knockdown of apicoplast FAS II in a mouse model results in cure from a lethal challenge infection. In conclusion, our study demonstrates a direct link between apicoplast FAS II functions and parasite survival and pathogenesis. Our genetic model also offers a platform to dissect the integration of the apicoplast into parasite metabolism, especially its postulated interaction with the mitochondrion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.