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 sy...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61155-9 |
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| author | Christophe-Sébastien Arnold Anna-Maria Alazzi Serena Shunmugam Jan Janouškovec Laurence Berry Sarah Charital Thierry Gautier Samuel Duley Delphine Jublot Catherine Lemaire-Vieille Marie-France Cesbron-Delauw Pierre Cavailles Jérôme Govin Nicholas J. Katris Yoshiki Yamaryo-Botté Cyrille Y. Botté |
| author_facet | Christophe-Sébastien Arnold Anna-Maria Alazzi Serena Shunmugam Jan Janouškovec Laurence Berry Sarah Charital Thierry Gautier Samuel Duley Delphine Jublot Catherine Lemaire-Vieille Marie-France Cesbron-Delauw Pierre Cavailles Jérôme Govin Nicholas J. Katris Yoshiki Yamaryo-Botté Cyrille Y. Botté |
| author_sort | Christophe-Sébastien Arnold |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4eddebe41ff04b46bc50544eb5287c4d |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4eddebe41ff04b46bc50544eb5287c4d2025-08-20T03:03:41ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-61155-9A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in ToxoplasmaChristophe-Sébastien Arnold0Anna-Maria Alazzi1Serena Shunmugam2Jan Janouškovec3Laurence Berry4Sarah Charital5Thierry Gautier6Samuel Duley7Delphine Jublot8Catherine Lemaire-Vieille9Marie-France Cesbron-Delauw10Pierre Cavailles11Jérôme Govin12Nicholas J. Katris13Yoshiki Yamaryo-Botté14Cyrille Y. Botté15Apicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesTeam Govin, Institute for Advanced Biosciences, CNRS UMR5309, INSERM U1209, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesCentre Algatech, Institute of Microbiology of the Czech Academy of SciencesLaboratory of Pathogen Host Interactions, Université MontpellierApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesTeam Govin, Institute for Advanced Biosciences, CNRS UMR5309, INSERM U1209, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesTeam Govin, Institute for Advanced Biosciences, CNRS UMR5309, INSERM U1209, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesApicolipid Team, Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble AlpesAbstract 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.https://doi.org/10.1038/s41467-025-61155-9 |
| spellingShingle | Christophe-Sébastien Arnold Anna-Maria Alazzi Serena Shunmugam Jan Janouškovec Laurence Berry Sarah Charital Thierry Gautier Samuel Duley Delphine Jublot Catherine Lemaire-Vieille Marie-France Cesbron-Delauw Pierre Cavailles Jérôme Govin Nicholas J. Katris Yoshiki Yamaryo-Botté Cyrille Y. Botté A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma Nature Communications |
| title | A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma |
| title_full | A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma |
| title_fullStr | A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma |
| title_full_unstemmed | A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma |
| title_short | A P5-ATPase, TgFLP12, diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in Toxoplasma |
| title_sort | p5 atpase tgflp12 diverging from plant chloroplast lipid transporters mediates apicoplast fatty export in toxoplasma |
| url | https://doi.org/10.1038/s41467-025-61155-9 |
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