{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:23:44Z","timestamp":1790663024374,"version":"4.1.0"},"reference-count":62,"publisher":"National Academy of Sciences","issue":"30","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["419345764"],"award-info":[{"award-number":["419345764"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KI2104"],"award-info":[{"award-number":["01KI2104"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017519","name":"Werner Otto Stiftung","doi-asserted-by":"publisher","award":["3\/102"],"award-info":[{"award-number":["3\/102"]}],"id":[{"id":"10.13039\/501100017519","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010438","name":"Francis Crick Institute","doi-asserted-by":"publisher","award":["CC2129"],"award-info":[{"award-number":["CC2129"]}],"id":[{"id":"10.13039\/100010438","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CSSB Seed grant","award":["KIF-2019\/002"],"award-info":[{"award-number":["KIF-2019\/002"]}]},{"DOI":"10.13039\/100010127","name":"J\u00fcrgen Manchot Stiftung","doi-asserted-by":"publisher","award":["stipend"],"award-info":[{"award-number":["stipend"]}],"id":[{"id":"10.13039\/100010127","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,7,25]]},"abstract":"<jats:p>\n                    To ensure their survival in the human bloodstream, malaria parasites degrade up to 80% of the host erythrocyte hemoglobin in an acidified digestive vacuole. Here, we combine conditional reverse genetics and quantitative imaging approaches to demonstrate that the human malaria pathogen\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    employs a heteromultimeric V-ATPase complex to acidify the digestive vacuole matrix, which is essential for intravacuolar hemoglobin release, heme detoxification, and parasite survival. We reveal an additional function of the membrane-embedded V-ATPase subunits in regulating morphogenesis of the digestive vacuole independent of proton translocation. We further show that intravacuolar accumulation of antimalarial chemotherapeutics is surprisingly resilient to severe deacidification of the vacuole and that modulation of V-ATPase activity does not affect parasite sensitivity toward these drugs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2306420120","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T13:35:13Z","timestamp":1689687313000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["The role of\n                    <i>Plasmodium<\/i>\n                    V-ATPase in vacuolar physiology and antimalarial drug uptake"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4918-4640","authenticated-orcid":false,"given":"Arne","family":"Alder","sequence":"first","affiliation":[{"name":"Cell Biology of Human Parasites Group, Centre for Structural Systems Biology, Hamburg 22607, Germany"},{"name":"Cellular Parasitology Department, Bernhard Nocht Institute for Tropical Medicine, Hamburg 20359, Germany"},{"name":"Department of Biology, University of Hamburg, Hamburg 20146, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-3726","authenticated-orcid":false,"given":"Cecilia P.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, Parasitology, Heidelberg University Hospital, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4608-7669","authenticated-orcid":false,"given":"Matthew R. G.","family":"Russell","sequence":"additional","affiliation":[{"name":"Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, United Kingdom"},{"name":"Centre for Ultrastructural Imaging, King\u2019s College London, London SE1 1UL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0260-613X","authenticated-orcid":false,"given":"Lucy M.","family":"Collinson","sequence":"additional","affiliation":[{"name":"Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lanzer","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, Parasitology, Heidelberg University Hospital, Heidelberg 69120, Germany"}],"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 NW1 1AT, United Kingdom"},{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene &amp; Tropical Medicine, London WC1E 7HT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim-Wolf","family":"Gilberger","sequence":"additional","affiliation":[{"name":"Cell Biology of Human Parasites Group, Centre for Structural Systems Biology, Hamburg 22607, Germany"},{"name":"Cellular Parasitology Department, Bernhard Nocht Institute for Tropical Medicine, Hamburg 20359, Germany"},{"name":"Department of Biology, University of Hamburg, Hamburg 20146, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0575-0412","authenticated-orcid":false,"given":"Joachim M.","family":"Matz","sequence":"additional","affiliation":[{"name":"Cell Biology of Human Parasites Group, Centre for Structural Systems Biology, Hamburg 22607, Germany"},{"name":"Cellular Parasitology Department, Bernhard Nocht Institute for Tropical Medicine, Hamburg 20359, Germany"},{"name":"Malaria Biochemistry Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0321-3"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.28.2.355"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.03.010"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2022.02.010"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2004.01.006"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601876103"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/35005132"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020793"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11865"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb300454t"},{"key":"e_1_3_4_11_2","first-page":"406","article-title":"Haemoglobin degradation underpins the sensitivity of early ring stage Plasmodium falciparum to artemisinins","volume":"129","author":"Xie S. C.","year":"2016","unstructured":"S. C. Xie , Haemoglobin degradation underpins the sensitivity of early ring stage Plasmodium falciparum to artemisinins. J. Cell Sci. 129, 406\u2013416 (2016).","journal-title":"J. Cell Sci."},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.016115"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(02)02365-6"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.8.2931"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0013501"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(86)90668-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1984.tb02195.x"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/235050a0"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2014.01.018"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14365"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.02.014"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108310200"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003323200"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507727200"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208648200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.47.33213"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7715"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20629-8"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00905-18"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113766"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.09143"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.10.4448.bloodjournal87104448"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00141"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02795"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00267-14"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1984.tb02981.x"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00088-14"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.030"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.038"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2013.10.014"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep29045"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413764111"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.335"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/35054500"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14441"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.9.2784"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90302-2"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058933"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01064"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.1.170"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.2.363"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.11.002"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.5.2652"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(98)00140-3"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601203"},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/j.1365-2958.2008.06413.x","article-title":"Polymorphisms within PfMDR1 alter the substrate specificity for anti-malarial drugs in Plasmodium falciparum","volume":"70","author":"Sanchez C. P.","year":"2008","unstructured":"C. P. Sanchez, A. Rotmann, W. D. Stein, M. Lanzer, Polymorphisms within PfMDR1 alter the substrate specificity for anti-malarial drugs in Plasmodium falciparum. Mol. Microbiol. 70, 786\u2013798 (2008).","journal-title":"Mol. Microbiol."},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001616"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/35002615"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11553"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02093-20"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0911317106"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2001153117"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2306420120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T03:04:51Z","timestamp":1702782291000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2306420120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,18]]},"references-count":62,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2023,7,25]]}},"alternative-id":["10.1073\/pnas.2306420120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2306420120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,18]]},"assertion":[{"value":"2023-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2306420120"}}