Apicomplexa are obligate intracellular parasites responsible for major human diseases such as toxoplasmosis, caused by Toxoplasma gondii (Tg.). Its intracellular survival is closely linked to fatty acids (FAs) acquisition and usage to produce essential complex lipids for membrane biogenesis, signal transduction, membrane stability and energy storage (1). To fulfil its needs in FAs, the parasite is able to produce some FAs de novo through the apicoplast FASII pathway as well as massively scavenging FAs from its host (1). To maintain this critical need for FA to maintain parasite propagation and to avoid their toxic accumulation, the trafficking of lipids is regulated by key proteins that act during their synthesis/import, their storage, and their transport between organelles (2). Endoplasmic reticulum (ER), Mitochondria (Mito) and Lipid droplets (LD) are key organelles for lipid trafficking and homeostasis. Recent work show that there is intense lipid exchanges happening between these organelles through membrane contact sites (MCSs) and specific lipid transfer proteins. In eukaryotic cells, ER MCSs involvement in lipid homeostasis have been shown to be pivotal for survival (3,4), these include ER-LD and ER-Mito. We have identified such pivotal LTPs, and we characterized the members of the Oxysterol Binding Protein Related Protein (ORP) in Toxoplasma. Among them proteins, we found that TgORP2 was located at the ER-Mito MCS and is responsible for lipid exchange between the two organelles. Here, I will be presenting my PhD project data deciphering on the key function of TgORP2 to maintain lipid trafficking and homeostasis, allowing parasite propagation during tachyzoite life stage.
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