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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F25%3A00637559" target="_blank" >RIV/61388971:_____/25:00637559 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-025-61155-9" target="_blank" >https://www.nature.com/articles/s41467-025-61155-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-025-61155-9" target="_blank" >10.1038/s41467-025-61155-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/GM21-19798M" target="_blank" >GM21-19798M: Biosyntéza a degradace fosfonátů – nová mitochondriální dráha podílející se na globálním koloběhu fosforu?</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

2041-1723

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

5538

Kód UT WoS článku

001523449800046

EID výsledku v databázi Scopus

2-s2.0-105009605917