title: Apicoplast-Localized Lysophosphatidic Acid Precursor Assembly Is Required for Bulk Phospholipid Synthesis in Toxoplasma gondii and Relies on an Algal/Plant-Like Glycerol 3-Phosphate Acyltransferase.
abstract: Most apicomplexan parasites possess a non-photosynthetic plastid (the apicoplast), which harbors enzymes for a number of metabolic pathways, including a prokaryotic type II fatty acid synthesis (FASII) pathway. In Toxoplasma gondii, the causative agent of toxoplasmosis, the FASII pathway is essential for parasite growth and infectivity. However, little is known about the fate of fatty acids synthesized by FASII. In this study, we have investigated the function of a plant-like glycerol 3-phosphate acyltransferase (TgATS1) that localizes to the T. gondii apicoplast. Knock-down of TgATS1 resulted in significantly reduced incorporation of FASII-synthesized fatty acids into phosphatidic acid and downstream phospholipids and a severe defect in intracellular parasite replication and survival. Lipidomic analysis demonstrated that lipid precursors are made in, and exported from, the apicoplast for de novo biosynthesis of bulk phospholipids. This study reveals that the apicoplast-located FASII and ATS1, which are primarily used to generate plastid galactolipids in plants and algae, instead generate bulk phospholipids for membrane biogenesis in T. gondii.
authors.affiliation: ApicoLipid group, Institute for Advanced Biosciences UMR5309, CNRS, Université Grenoble Alpes, INSERM, Grenoble, France.
authors.forename: Souad
authors.initials: S
authors.lastname: Amiar
authors.affiliation: The Francis Crick Institute, The Ridgeway, Mill Hill, London, United Kingdom.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: James I
authors.initials: JI
authors.lastname: MacRae
authors.affiliation: Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Deakin University, Burwood, Victoria, Australia.|School of BioSciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Damien L
authors.initials: DL
authors.lastname: Callahan
authors.affiliation: ApicoLipid group, Institute for Advanced Biosciences UMR5309, CNRS, Université Grenoble Alpes, INSERM, Grenoble, France.
authors.forename: David
authors.initials: D
authors.lastname: Dubois
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: Giel G
authors.initials: GG
authors.lastname: van Dooren
authors.affiliation: ApicoLipid group, Institute for Advanced Biosciences UMR5309, CNRS, Université Grenoble Alpes, INSERM, Grenoble, France.|School of BioSciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Shears
authors.affiliation: BNI group, TIMC-IMAG UMR5525 CNRS, Université Grenoble Alpes, Grenoble, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Cesbron-Delauw
authors.affiliation: Unité de recherche (UMR) 5168, CNRS, CEA, INRA, Université Grenoble Alpes, Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Maréchal
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science & Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: McConville
authors.affiliation: School of BioSciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
authors.affiliation: ApicoLipid group, Institute for Advanced Biosciences UMR5309, CNRS, Université Grenoble Alpes, INSERM, Grenoble, France.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaryo-Botté
authors.affiliation: ApicoLipid group, Institute for Advanced Biosciences UMR5309, CNRS, Université Grenoble Alpes, INSERM, Grenoble, France.
authors.forename: Cyrille Y
authors.initials: CY
authors.lastname: Botté
mesh_terms: D000595:Amino Acid Sequence; D063546:Apicoplasts / Q000201:enzymology*; D002853:Chromatography, Liquid; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D008246:Lysophospholipids / Q000096:biosynthesis; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D010743:Phospholipids / Q000096:biosynthesis*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000737:chemistry; D014122:Toxoplasma / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D010743:Phospholipids; D015800:Protozoan Proteins; D005992:Glycerol-3-Phosphate O-Acyltransferase; C032881:lysophosphatidic acid