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Here, we localize\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    patatin-like phospholipase 2 (\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2, PF3D7_1358000) to the mitochondrion and reveal that disruption of the\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2 gene impairs asexual replication.\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2-null parasites are hypersensitive to proguanil and inhibitors of the mitochondrial ETC, including atovaquone. In addition,\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2-deficient parasites show reduced mitochondrial respiration and reduced mitochondrial membrane potential, indicating that disruption of\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2 leads to a defect in the parasite ETC. Lipidomic analysis of the mitochondrial phospholipid cardiolipin (CL) reveals that loss of\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2 is associated with a moderate shift toward shorter-chained and more saturated CL species, implying a contribution of\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2 to CL remodeling.\n                    <jats:italic>Pf<\/jats:italic>\n                    PNPLA2-deficient parasites display profound defects in gametocytogenesis, underlining the importance of a functional mitochondrial ETC during both the asexual and sexual development of the parasite.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      For their proliferation within red blood cells, malaria parasites depend on a functional electron transport chain (ETC) within their mitochondrion, which is the target of several antimalarial drugs. Here, we have used gene disruption to identify a patatin-like phospholipase,\n                      <jats:italic>Pf<\/jats:italic>\n                      PNPLA2, as important for parasite replication and mitochondrial function in\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      . Parasites lacking\n                      <jats:italic>Pf<\/jats:italic>\n                      PNPLA2 show defects in their ETC and become hypersensitive to mitochondrion-targeting drugs. Furthermore,\n                      <jats:italic>Pf<\/jats:italic>\n                      PNPLA2-deficient parasites show differences in the composition of their cardiolipins, a unique class of phospholipids with key roles in mitochondrial functions. Finally, we demonstrate that parasites devoid of\n                      <jats:italic>Pf<\/jats:italic>\n                      PNPLA2 have a defect in gametocyte maturation, underlining the importance of a functional ETC for parasite transmission to the mosquito vector.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01718-23","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T09:00:46Z","timestamp":1698310846000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["A patatin-like phospholipase is important for mitochondrial function in malaria parasites"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4744-1666","authenticated-orcid":false,"given":"Emma","family":"Pietsch","sequence":"first","affiliation":[{"name":"Centre for Structural Systems Biology, Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9372-5526","authenticated-orcid":false,"given":"Abhinay","family":"Ramaprasad","sequence":"additional","affiliation":[{"name":"Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Bielfeld","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology, Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0988-9411","authenticated-orcid":false,"given":"Yvonne","family":"Wohlfarter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8444-313X","authenticated-orcid":false,"given":"Bohumil","family":"Maco","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korbinian","family":"Niederm\u00fcller","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology, Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-272X","authenticated-orcid":false,"given":"Louisa","family":"Wilcke","sequence":"additional","affiliation":[{"name":"Centre for Structural Systems Biology, Hamburg, Germany"},{"name":"Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany"},{"name":"University of Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-8599","authenticated-orcid":false,"given":"Joachim","family":"Kloehn","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-9920","authenticated-orcid":false,"given":"Markus A.","family":"Keller","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-2109","authenticated-orcid":true,"given":"Dominique","family":"Soldati-Favre","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7442-3810","authenticated-orcid":false,"given":"Michael J.","family":"Blackman","sequence":"additional","affiliation":[{"name":"Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United Kingdom"},{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene &amp; 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