2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sheena Dass ◽  
Serena Shunmugam ◽  
Laurence Berry ◽  
Christophe-Sebastien Arnold ◽  
Nicholas J. Katris ◽  
...  

AbstractApicomplexa 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.


2004 ◽  
Vol 82 (1) ◽  
pp. 156-169 ◽  
Author(s):  
Dennis R Voelker

Inter- and intramembrane phospholipid transport processes are central features of membrane biogenesis and homeostasis. Relatively recent successes in the molecular genetic analysis of aminoglycerophospholipid transport processes in both yeast and mammalian cells are now providing important new information defining specific protein and lipid components that participate in these reactions. Studies focused on phosphatidylserine (PtdSer) transport to the mitochondria reveal that the process is regulated by ubiquitination. In addition, a specific mutation disrupts PtdSer transport between mitochondrial membranes. Analysis of PtdSer transport from the endoplasmic reticulum to the locus of PtdSer decarboxylase 2 demonstrates the requirement for a phosphatidylinositol-4-kinase, a phosphatidylinositol-binding protein, and the C2 domain of the decarboxylase. Examination of NBD-phosphatidylcholine transport demonstrates the involvement of the prevacuolar compartment and a requirement for multiple genes involved in regulating vacuolar protein sorting for transport of the lipid to the vacuole. In intramembrane transport, multiple genes are now identified including those encoding multidrug resistant protein family members, DNF family members, ATP binding cassette transporters, and pleiotropic drug resistance family members. The scramblase family constitutes a collection of putative transmembrane transporters that function in an ATP-independent manner. The genetic analysis of lipid traffic is uncovering new molecules involved in all aspects of the regulation and execution of the transport steps and also providing essential tools to critically test the involvement of numerous candidate molecules.Key words: lipid transport, lipid sorting, membrane biogenesis, organelles, flippase.


1988 ◽  
Vol 27 (6) ◽  
pp. 1631-1638 ◽  
Author(s):  
Patrick Moreau ◽  
Hélène Juguelin ◽  
René Lessire ◽  
Claude Cassagne

1982 ◽  
Vol 152 (2) ◽  
pp. 607-615
Author(s):  
B D Cain ◽  
T J Donohue ◽  
S Kaplan

The accumulation of N-acylphosphatidylserine (NAPS) in response to the inclusion of Tris in the growth medium of Rhodopseudomonas sphaeroides strain M29-5 has been examined. In the accompanying paper (Donohue et al., J. Bacteriol. 152:000--000, 1982), we show that in response to Tris, NAPS accumulated to as much as 40% of the total cellular phospholipid content. NAPS accumulation began immediately upon addition of Tris and was reflected as an abrupt 12-fold increase in the apparent rate of NAPS accumulation. We suggest that Tris altered the flow of metabolites through a preexisting and previously unknown metabolic pathway. NAPS accumulation ceased immediately upon the removal of Tris; however, accumulated NAPS remained largely metabolically stable. Importantly, under conditions in which NAPS was not accumulated, the intracytoplasmic membrane was shown to be virtually devoid of newly synthesized NAPS. The significance of this observation is discussed in terms of its physiological implications on phospholipid transfer and membrane biogenesis in R. sphaeroides.


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