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In the malaria-causing parasite Plasmodium falciparum the roles of LDs in lipid acquisition from its host cells and their metabolism are poorly understood, despite the high demand for lipids in parasite membrane synthesis. We systematically characterised LD size, composition and dynamics across the disease-causing blood infection. Applying split fluorescence emission analysis and three-dimensional (3D) focused ion beam-scanning electron microscopy (FIB-SEM), we observed a decrease in LD size in late schizont stages. LD contraction likely signifies a switch from lipid accumulation to lipid utilisation in preparation for parasite egress from host red blood cells. We demonstrate connections between LDs and several parasite organelles, pointing to potential functional interactions. Chemical inhibition of triacylglyerol (TAG) synthesis or breakdown revealed essential LD functions for schizogony and in counteracting lipid toxicity. The dynamics of lipid synthesis, storage and utilisation in P. falciparum LDs might provide a target for new anti-malarial intervention strategies.<\/jats:p>","DOI":"10.1242\/jcs.262162","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T10:16:52Z","timestamp":1720088212000},"source":"Crossref","is-referenced-by-count":7,"title":["Lipid droplet dynamics are essential for the development of the malaria parasite <i>Plasmodium falciparum<\/i>"],"prefix":"10.1242","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-2106","authenticated-orcid":false,"given":"Jiwon","family":"Lee","sequence":"first","affiliation":[{"name":"Centre for Advanced Microscopy, The Australian National University 1 , Canberra ACT, 2601 , Australia"},{"name":"Research School of Biology, The Australian National University 2 , Canberra ACT, 2601 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6147-8591","authenticated-orcid":false,"given":"Kai","family":"Matuschewski","sequence":"additional","affiliation":[{"name":"3 Molecular Parasitology, Humboldt University, 10099 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-9821","authenticated-orcid":false,"given":"Giel","family":"van Dooren","sequence":"additional","affiliation":[{"name":"Research School of Biology, The Australian National University 2 , Canberra ACT, 2601 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7369-1058","authenticated-orcid":false,"given":"Alexander G.","family":"Maier","sequence":"additional","affiliation":[{"name":"Research School of Biology, The Australian National University 2 , Canberra ACT, 2601 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4687-9677","authenticated-orcid":false,"given":"Melanie","family":"Rug","sequence":"additional","affiliation":[{"name":"Centre for Advanced Microscopy, The Australian National University 1 , Canberra ACT, 2601 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"2024080813583217000_JCS262162C1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/BF00281808","article-title":"Osmium tetroxide as a histochemical and histological reagent","volume":"9","author":"Adams","year":"1967","journal-title":"Histochemie"},{"key":"2024080813583217000_JCS262162C2","doi-asserted-by":"crossref","DOI":"10.1515\/9783112366967","volume-title":"Die Elementarorganismen und ihre Beziehungen zu den Zellen: Veit & Comp","author":"Altmann","year":"1894"},{"key":"2024080813583217000_JCS262162C3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1186\/1475-2875-11-337","article-title":"Neutral lipids associated with haemozoin mediate efficient and rapid \u03b2-haematin formation at physiological pH, temperature and ionic composition","volume":"11","author":"Ambele","year":"2012","journal-title":"Malar. 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