Membrane Contact Sites between Apicoplast and ER in <i>Toxoplasma gondii</i> Revealed by Electron Tomography

Tomova, Cveta; Humbel, Bruno M.; Geerts, Willie J. C.; Entzeroth, Rolf; Holthuis, Joost C. M.; Verkleij, Arie J.

doi:10.1111/j.1600-0854.2009.00954.x

Cited by 60 publications

(44 citation statements)

References 73 publications

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“…3B), which could have been generated during the purification/extraction procedure but could also reflect continuous remodeling of apicoplast phospholipids by lysophospholipases and acylglycerol-phosphate acyltransferases with neighboring ER (6,47).…”

Section: Resultsmentioning

confidence: 99%

Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites

Botté

Yamaryo‐Botté

Rupasinghe

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

125

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The human malaria parasite Plasmodium falciparum harbors a relict, nonphotosynthetic plastid of algal origin termed the apicoplast. Although considerable progress has been made in defining the metabolic functions of the apicoplast, information on the composition and biogenesis of the four delimiting membranes of this organelle is limited. Here, we report an efficient method for preparing highly purified apicoplasts from red blood cell parasite stages and the comprehensive lipidomic analysis of this organelle. Apicoplasts were prepared from transgenic parasites expressing an epitope-tagged triosephosphate transporter and immunopurified on magnetic beads. Gas and liquid chromatography MS analyses of isolated apicoplast lipids indicated significant differences compared with total parasite lipids. In particular, apicoplasts were highly enriched in phosphatidylinositol, consistent with a suggested role for phosphoinositides in targeting membrane vesicles to apicoplasts. Apicoplast phosphatidylinositol and other phospholipids were also enriched in saturated fatty acids, which could reflect limited acyl exchange with other membrane phospholipids and/or a requirement for specific physical properties. Lipids atypical for plastids (sphingomyelins, ceramides, and cholesterol) were detected in apicoplasts. The presence of cholesterol in apicoplast membranes was supported by filipin staining of isolated apicoplasts. Galactoglycerolipids, dominant in plant and algal plastids, were not detected in P. falciparum apicoplasts, suggesting that these glycolipids are a hallmark of photosynthetic plastids and were lost when these organisms assumed a parasitic lifestyle. Apicoplasts thus contain an atypical melange of lipids scavenged from the human host alongside lipids remodeled by the parasite cytoplasm, and stable isotope labeling shows some apicoplast lipids are generated de novo by the organelle itself.

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Section: Resultsmentioning

confidence: 99%

Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites

Botté

Yamaryo‐Botté

Rupasinghe

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

122

125

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“…As ACS enzymes catalyze the transfer of free fatty acids to CoA, this process is reliant on an acyl-ACP thioesterase, which releases fatty acids from ACP to permit their diffusion across the inner chloroplast membrane [178,179]. The discovery of similar membrane contact sites between the apicoplast and ER in Plasmodium and T. gondii [180,181] support the presence of an equivalent pathway in parasites, and metabolic labeling has given direct evidence for FASII fatty acid export in Toxoplasma [111]. However, as no candidate apicoplast acyl-ACP thioesterase can be identified in either P. falciparum or T. gondii [26,31], it is not clear how free fatty acids might be generated for the apicoplast ACS enzymes (Fig.…”

Section: Acyl-coa Synthetases (Acs)mentioning

confidence: 98%

Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts

Shears

Botté

McFadden

2015

Molecular and Biochemical Parasitology

104

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The malaria parasite Plasmodium possesses a relict, non-photosynthetic plastid known as the apicoplast. The apicoplast is essential for parasite survival, and harbors several plant-like metabolic pathways including a type II fatty acid synthesis (FASII) pathway. The FASII pathway was discovered in 1998, and much of the early research in the field pursued it as a therapeutic drug target. These studies identified a range of compounds with activity against bloodstage parasites and led to the localization and characterization of most enzymes in the pathway. However, when genetic studies revealed FASII was dispensable in bloodstage parasites, it effectively discounted the pathway as a therapeutic drug target, and suggested these compounds instead interfered with other processes. Interest in FASII then shifted toward its disruption for malaria prophylaxis and vaccine development, with experiments in rodent malaria models identifying a crucial role for the pathway in the parasite's transition from the liver to the blood. Unexpectedly however, the human malaria parasite P. falciparum was recently found to differ from rodent models and require FASII for mosquito stage development. This requirement blocked the production of the FASII-deficient forms that might be used as a genetically attenuated parasite vaccine, suggesting the pathway was also unsuitable as a vaccine target. This review discusses how perception of FASII has changed over time, and presents key findings about each enzyme in the pathway to identify remaining questions and opportunities for malaria control.

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“…In gametocytes, the apicoplast and mitochondria are closely associated, although the mitochondria undergoes significant morphological changes whereas the apicoplast remains relatively quiescent [18]. In the related apicomplexan T. gondii, a tight association between the apicoplast and ER is also observed [19], whereas apicoplast elongation and division appears to be tightly associated with the daughter cell formation [20,21].…”

Section: The Essential and Dynamic Apicoplast Of P Falciparummentioning

confidence: 94%

Malaria, Plasmodium falciparum and its apicoplast

Kalanon

McFadden

2010

Biochemical Society Transactions

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Malaria, which is caused by species of the parasite genus Plasmodium, remains a major global health problem. A vestigial plastid homologous with the chloroplasts of plants and algae was discovered in malaria and related parasites from the phylum Apicomplexa and has radically changed our view of the evolutionary origins of these disease-causing protists. We now recognize that this large group of parasites had a photosynthetic ancestry and were converted into parasitism early in the evolution of animals. Apicomplexans have probably been parasitizing the animal kingdom for more than 500 million years. The relic plastid persists in most apicomplexans and is an essential component. Perturbation of apicoplast function or inheritance results in parasite death, making the organelle a promising target for chemotherapy. Plastids, including those of malaria parasites, are essentially reduced endosymbiotic bacteria living inside a eukaryotic host. This means that plastids have bacterial-type metabolic pathways and housekeeping processes, all of which are vulnerable to antibacterial compounds. Indeed, many antibacterials kill malaria parasites by blocking essential processes in the plastid. Furthermore, a range of herbicides that target plastid metabolism of undesired plants are also parasiticidal, making them potential new leads for antimalarial drugs. In the present review, we examine the evolutionary origins of the malaria parasite's plastid by endosymbiosis and outline the recent findings on how the organelle imports nuclear-encoded proteins through a set of translocation machineries in the membranes that bound the organelle.

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Membrane Contact Sites between Apicoplast and ER in Toxoplasma gondii Revealed by Electron Tomography

Cited by 60 publications

References 73 publications

Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites

Atypical lipid composition in the purified relict plastid (apicoplast) of malaria parasites

Fatty acid metabolism in the Plasmodium apicoplast: Drugs, doubts and knockouts

Malaria, Plasmodium falciparum and its apicoplast

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