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

Abstract

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.

Light Remodels Lipid Biosynthesis in Nannochloropsis gaditana by Modulating Carbon Partitioning between Organelles

“…In primary chloroplasts, DHAP is known to be exported to the cytosol by the triose phosphate/ phosphate translocator (TPT) in exchange for inorganic phosphate (Pi) needed to regenerate ATP in the stroma. In the secondary plastid of Apicomplexa (organisms presenting a plastid limited by four membranes, as in Eustigmatophyceae, but lacking photosynthesis), TPT translocators act in the opposite way, importing DHAP to feed the nonmevalonate pathway of isoprenoid synthesis and FA synthesis (Mullin et al, 2006;Brooks et al, 2010;Botté et al, 2012Botté et al, , 2013. We identified four genes coding for TPTs in N. gaditana (Naga_100100g11, Naga_101308g1, Naga_100006g37, and Naga_100007g104), and at least one of these genes has high homology with the Apicomplexa TPT (Naga_100100g11), showing conserved features such as 10 membrane-spanning domains and a chloroplastic transit peptide, suggesting a likely similar role in importing DHAP into the plastid.…”

Isoprenoid Precursor Biosynthesis Is the Essential Metabolic Role of the Apicoplast during Gametocytogenesis in Plasmodium falciparum

“…The apicoplast supports three metabolic functions: type II fatty acid biosynthesis, de novo heme biosynthesis, and isoprenoid biosynthesis. Type II fatty acid and de novo heme biosynthesis are not essential during the asexual and gametocyte intraerythrocytic stages when parasites scavenge lipids and heme from the human host (15)(16)(17); however, both of these biosynthetic pathways are essential for development of liver and mosquito stages of the parasite (15)(16)(17)(18)(19)(20). In contrast, biosynthesis of the isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) is the essential metabolic function of the apicoplast in the asexual intraerythrocytic stages (21).…”

Phospholipases during membrane dynamics in malaria parasites

“…The membrane composition of RBC-freed malaria parasites is primarily composed of PLs like PC (∼40%) and PE (∼30%). The amount of SM (∼15%) in the parasites is comparable to that of uRBCs, while PS (∼5%) and PE plasmalogen (∼10%) are found at lower concentrations (Botté et al, 2013;Gulati et al, 2015;reviewed in Vial et al, 2003). Cholesterol is almost absent in the membranes of Plasmodium parasites, related to its inability to synthesize sterols (reviewed in Déchamps et al, 2010;Vial et al, 2003;Vial and Ancelin, 1992).…”

“…A recent study reported the successful purification of this plastid, allowing the authors to determine its lipid content. They found that the apicoplast is enriched in PIs, particularly PI3-phosphate, as well as in other PLs having saturated FAs, suggesting limited acyl exchange with other membrane PLs or the requirement for specific physical properties in the apicoplast (Botté et al, 2013;Tawk et al, 2010). Interestingly, the apicoplast also features lipids atypical for plastids, such as SM, ceramides and cholesterol.…”

“…Interestingly, the apicoplast also features lipids atypical for plastids, such as SM, ceramides and cholesterol. These lipids were suggested to contribute to changes in multi-membrane properties affecting both permeability and the activity of integral membrane transporter proteins (Botté et al, 2013).…”