A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma

Abstract

Toxoplasma gondii, an apicomplexan parasite and agent of the human disease toxoplasmosis, possesses a non-photosynthetic relic plastid, named the apicoplast. Thought to be evolved from a red algal plastid, the apicoplast houses major metabolic pathways, such as heme, isoprenoid and lipid synthesis, crucial for parasite survival, and thus considered attractive drug targets. However, despite similarities with plant chloroplast lipid synthesis pathways, the apicoplast lacks canonical plant/chloroplast lipid transporters and so metabolite import/export is at present, poorly characterised. Here we identify TgFLP12, a newly identified P5-ATPase transporter localised to the Toxoplasma apicoplast. TgFLP12 is found in the SAR (Stramenopile-Alveolata-Rhizaria) supergroup (to which belong Apicomplexa parasites and chromerids) but absent in higher plants. Disruption of TgFLP12 causes major defects on apicoplast morphology. Lipidomic analyses and stable isotope labelling reveal a unique accumulation of C14:0 in the apicoplast, which is then lacking in most major lipid classes subsequently synthesized in the ER. Successful complementation of a yeast mutant deficient in fatty acid transport with TgFLP12 validates TgFLP12 as a fatty acid transporter. Overall, we identify a potentially important drug target: the apicoplast fatty acid exporter, specific to Apicomplexa which unexpectedly also highlights Toxoplasma’s utility as a model organism for investigating algal biology.

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