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The parasite digests the host cell cytoplasm in its food vacuole, a pathway of particular interest as drug target. The Vps34-type PI3-kinase in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    produces PI3-monophophate (PI3P) and has been linked to haemoglobin digestion, to resistance to the current first line antimalarial artemisinin and to biology of the apicoplast. Here we dissect the functions of\n                    <jats:italic>Pf<\/jats:italic>\n                    PI3-kinase by inducible deletion of its gene using the\n                    <jats:italic>loxP<\/jats:italic>\n                    -DiCre system and find that\n                    <jats:italic>Pf<\/jats:italic>\n                    PI3-kinase is essential for parasite survival. Mutant parasites accumulate undigested haemoglobin (Hb) confirming a defect in the pathway of Hb uptake and digestion, the most likely reason for parasite death. Some parasites are affected in apicoplast inheritance demonstrating that PI3P-dependent processes are important for apicoplast biology in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . Finally, we discover that in PI3-kinase mutant parasites carrying a mutation conferring resistance to artemisinin, the lower amounts of PI3P correlate with lower levels of artemisinin resistance. We suggest that the reduced levels of PI3P in the PI3-kinase mutant dampen repair mechanisms like the autophagic processes normally associated with Kelch13 mutations, leading to a proteotoxic stress and to an increase in susceptibility to artemisinin.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-01397-1","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T05:07:06Z","timestamp":1747199226000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PI3-kinase has multiple functions in asexual blood stages of Plasmodium falciparum"],"prefix":"10.1038","volume":"15","author":[{"given":"Reem","family":"Al Monla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Penzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Vallentin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakhee","family":"Lohia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rita","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Cerdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wengelnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"1397_CR1","unstructured":"World Health Organisation. 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