{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:57:51Z","timestamp":1789441071153,"version":"build-2803163510"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM133764"],"award-info":[{"award-number":["R35GM133764"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000875","name":"Pew Charitable Trusts","doi-asserted-by":"publisher","award":["32099"],"award-info":[{"award-number":["32099"]}],"id":[{"id":"10.13039\/100000875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI055434"],"award-info":[{"award-number":["T32AI055434"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Isoprenoid precursor synthesis is an ancient and fundamental function of plastid organelles and a critical metabolic activity of the apicoplast in\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    malaria parasites [1\u20133]. Over the past decade, our understanding of apicoplast properties and functions has increased enormously [4], due in large part to our ability to rescue blood-stage parasites from apicoplast-specific dysfunctions by supplementing cultures with isopentenyl pyrophosphate (IPP), a key output of this organelle [5,6]. In this Pearl, we explore the interdependence between isoprenoid metabolism and apicoplast biogenesis in\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    and highlight critical future questions to answer.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011713","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T13:21:30Z","timestamp":1698326490000},"page":"e1011713","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites"],"prefix":"10.1371","volume":"19","author":[{"given":"Megan","family":"Okada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-3042","authenticated-orcid":true,"given":"Paul A.","family":"Sigala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"issue":"33","key":"ppat.1011713.ref001","doi-asserted-by":"crossref","first-page":"10200","DOI":"10.1073\/pnas.1423790112","article-title":"Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives","volume":"112","author":"J Janouskovec","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ppat.1011713.ref002","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1128\/EC.00160-14","article-title":"Isoprenoid biosynthesis in Plasmodium falciparum","volume":"13","author":"AM Guggisberg","year":"2014","journal-title":"Eukaryot Cell"},{"issue":"3","key":"ppat.1011713.ref003","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrmicro843","article-title":"Tropical infectious diseases: metabolic maps and functions of the Plasmodium falciparum apicoplast","volume":"2","author":"SA Ralph","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1011713.ref004","doi-asserted-by":"crossref","first-page":"102255","DOI":"10.1016\/j.mib.2022.102255","article-title":"New insights into apicoplast metabolism in blood-stage malaria parasites","volume":"71","author":"R Elahi","year":"2023","journal-title":"Curr Opin Microbiol"},{"issue":"8","key":"ppat.1011713.ref005","doi-asserted-by":"crossref","first-page":"e1001138","DOI":"10.1371\/journal.pbio.1001138","article-title":"Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum","volume":"9","author":"E Yeh","year":"2011","journal-title":"PLoS Biol"},{"issue":"2","key":"ppat.1011713.ref006","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1128\/EC.00198-14","article-title":"Isoprenoid precursor biosynthesis is the essential metabolic role of the apicoplast during gametocytogenesis in Plasmodium falciparum","volume":"14","author":"JD Wiley","year":"2015","journal-title":"Eukaryot Cell"},{"key":"ppat.1011713.ref007","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.84491","article-title":"The Plasmodium falciparum apicoplast cysteine desulfurase provides sulfur for both iron-sulfur cluster assembly and tRNA modification.","volume":"12","author":"RP Swift","year":"2023","journal-title":"Elife"},{"issue":"6","key":"ppat.1011713.ref008","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1128\/AAC.02711-13","article-title":"Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition","volume":"58","author":"M Charan","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"ppat.1011713.ref009","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.pt.2018.05.010","article-title":"Recent Advances in the [Fe-S] Cluster Biogenesis (SUF) Pathway Functional in the Apicoplast of Plasmodium.","volume":"34","author":"ZR Pala","year":"2018","journal-title":"Trends Parasitol"},{"issue":"2","key":"ppat.1011713.ref010","doi-asserted-by":"crossref","first-page":"e89718","DOI":"10.1371\/journal.pone.0089718","article-title":"Identification of vital and dispensable sulfur utilization factors in the Plasmodium apicoplast.","volume":"9","author":"JM Haussig","year":"2014","journal-title":"PLoS ONE."},{"key":"ppat.1011713.ref011","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.50807","article-title":"The NTP generating activity of pyruvate kinase II is critical for apicoplast maintenance in Plasmodium falciparum.","volume":"9","author":"RP Swift","year":"2020","journal-title":"Elife"},{"issue":"7","key":"ppat.1011713.ref012","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1084\/jem.20110039","article-title":"Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii","volume":"208","author":"SC Nair","year":"2011","journal-title":"J Exp Med"},{"issue":"2","key":"ppat.1011713.ref013","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1128\/AAC.01500-13","article-title":"Antiapicoplast and gametocytocidal screening to identify the mechanisms of action of compounds within the malaria box","volume":"58","author":"JD Bowman","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"ppat.1011713.ref014","doi-asserted-by":"crossref","first-page":"e91178","DOI":"10.1371\/journal.pone.0091178","article-title":"Ycf93 (Orf105), a small apicoplast-encoded membrane protein in the relict plastid of the malaria parasite Plasmodium falciparum that is conserved in Apicomplexa.","volume":"9","author":"CD Goodman","year":"2014","journal-title":"PLoS ONE"},{"key":"ppat.1011713.ref015","doi-asserted-by":"crossref","first-page":"eLife.73208","DOI":"10.7554\/eLife.73208","article-title":"Critical role for isoprenoids in apicoplast biogenesis by malaria parasites.","volume":"11","author":"M Okada","year":"2022","journal-title":"Elife"},{"issue":"2","key":"ppat.1011713.ref016","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.abb.2011.10.018","article-title":"At the membrane frontier: a prospectus on the remarkable evolutionary conservation of polyprenols and polyprenyl-phosphates","volume":"517","author":"MD Hartley","year":"2012","journal-title":"Arch Biochem Biophys"},{"issue":"3","key":"ppat.1011713.ref017","article-title":"The Membrane Steps of Bacterial Cell Wall Synthesis as Antibiotic Targets.","volume":"5","author":"Y Liu","year":"2016","journal-title":"Antibiotics (Basel)."},{"issue":"24","key":"ppat.1011713.ref018","doi-asserted-by":"crossref","first-page":"13719","DOI":"10.1073\/pnas.1919501117","article-title":"Plastid biogenesis in malaria parasites requires the interactions and catalytic activity of the Clp proteolytic system","volume":"117","author":"A Florentin","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"16","key":"ppat.1011713.ref019","doi-asserted-by":"crossref","first-page":"e107247","DOI":"10.15252\/embj.2020107247","article-title":"Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption","volume":"40","author":"RP Swift","year":"2021","journal-title":"EMBO J"},{"issue":"6","key":"ppat.1011713.ref020","doi-asserted-by":"crossref","first-page":"e12947","DOI":"10.1111\/jeu.12947","article-title":"Roles of the apicoplast across the life cycles of rodent and human malaria parasites","volume":"69","author":"HD Buchanan","year":"2022","journal-title":"J Eukaryot Microbiol"},{"issue":"51","key":"ppat.1011713.ref021","doi-asserted-by":"crossref","first-page":"36338","DOI":"10.1074\/jbc.M113.503557","article-title":"Kinetic flux profiling elucidates two independent acetyl-CoA biosynthetic pathways in Plasmodium falciparum","volume":"288","author":"SA Cobbold","year":"2013","journal-title":"J Biol Chem"},{"issue":"5","key":"ppat.1011713.ref022","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1128\/EC.00264-13","article-title":"Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes","volume":"13","author":"BC van Schaijk","year":"2014","journal-title":"Eukaryot Cell"},{"issue":"5","key":"ppat.1011713.ref023","doi-asserted-by":"crossref","first-page":"e0196622","DOI":"10.1128\/mbio.01966-22","article-title":"The Heptaprenyl Diphosphate Synthase (Coq1) Is the Target of a Lipophilic Bisphosphonate That Protects Mice against Toxoplasma gondii Infection.","volume":"13","author":"MA Sleda","year":"2022","journal-title":"mBio"},{"issue":"5","key":"ppat.1011713.ref024","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.chom.2020.09.011","article-title":"A Comprehensive Subcellular Atlas of the Toxoplasma Proteome via hyperLOPIT Provides Spatial Context for Protein Functions","volume":"28","author":"K Barylyuk","year":"2020","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1011713.ref025","doi-asserted-by":"crossref","first-page":"101468","DOI":"10.1016\/j.jbc.2021.101468","article-title":"Toxoplasma gondii apicoplast-resident ferredoxin is an essential electron transfer protein for the MEP isoprenoid-biosynthetic pathway","volume":"298","author":"S Henkel","year":"2022","journal-title":"J Biol Chem"},{"issue":"Pt 1","key":"ppat.1011713.ref026","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1042\/BJ20050441","article-title":"Identification, molecular cloning and functional characterization of an octaprenyl pyrophosphate synthase in intra-erythrocytic stages of Plasmodium falciparum","volume":"392","author":"D Tonhosolo R","year":"2005","journal-title":"Biochem J"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011713","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T13:21:56Z","timestamp":1698326516000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011713"}},"subtitle":[],"editor":[{"given":"Audrey Ragan","family":"Odom John","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011713","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,26]]}}}