Toxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage

Sheena Dass, Serena Shunmugam, Laurence Berry, Christophe-Sebastien Arnold, Nicholas J. Katris, Samuel Duley, Fabien Pierrel, Marie-France Cesbron-Delauw, Yoshiki Yamaryo-Botté () and Cyrille Y. Botté ()
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Sheena Dass: Université Grenoble Alpes, INSERM U1209
Serena Shunmugam: Université Grenoble Alpes, INSERM U1209
Laurence Berry: Université de Montpellier
Christophe-Sebastien Arnold: Université Grenoble Alpes, INSERM U1209
Nicholas J. Katris: Université Grenoble Alpes, INSERM U1209
Samuel Duley: Université Grenoble Alpes, INSERM U1209
Fabien Pierrel: Université Grenoble Alpes, CNRS, Grenoble INP, TIMC-IMAG
Marie-France Cesbron-Delauw: Université Grenoble Alpes, INSERM U1209
Yoshiki Yamaryo-Botté: Université Grenoble Alpes, INSERM U1209
Cyrille Y. Botté: Université Grenoble Alpes, INSERM U1209

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Apicomplexa are obligate intracellular parasites responsible for major human diseases. Their intracellular survival relies on intense lipid synthesis, which fuels membrane biogenesis. Parasite lipids are generated as an essential combination of fatty acids scavenged from the host and de novo synthesized within the parasite apicoplast. The molecular and metabolic mechanisms allowing regulation and channeling of these fatty acid fluxes for intracellular parasite survival are currently unknown. Here, we identify an essential phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as the central metabolic nexus responsible for controlled lipid synthesis sustaining parasite development. Lipidomics reveal that TgLIPIN controls the synthesis of diacylglycerol and levels of phosphatidic acid that regulates the fine balance of lipids between storage and membrane biogenesis. Using fluxomic approaches, we uncover the first parasite host-scavenged lipidome and show that TgLIPIN prevents parasite death by ‘lipotoxicity’ through effective channeling of host-scavenged fatty acids to storage triacylglycerols and membrane phospholipids.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22956-w

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DOI: 10.1038/s41467-021-22956-w

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