{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T04:03:50Z","timestamp":1743307430642,"version":"3.40.3"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17K07771"],"award-info":[{"award-number":["JP17K07771"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Plasmodium falciparum is a major cause of severe malaria. This protozoan infects human red blood cells and secretes large quantities of histidine-rich protein 2 (PfHRP2) into the bloodstream, making it a well-known diagnostic marker. Here, however, we identified PfHRP2 as a pathogenic factor produced by P. falciparum. PfHRP2 showed cell penetration and cytotoxicity against various human cells. PfHRP2 also exhibited significant cytotoxicity at concentrations found in P. falciparum-infected patients' blood (90-100\u00a0n\u2009m). We also showed that PfHRP2 binds to Ca2+ ions, localizes to intracellular lysosomes, increases lysosomal Ca2+ levels, and inhibits the basal level of autophagy by preventing autolysosome formation. Furthermore, the Ca2+-dependent cytotoxicity of PfHRP2 was suppressed by the metal ion chelator ethylenediaminetetraacetic acid. In summary, our findings suggest PfHRP2 as a crucial pathogenic factor produced by P. falciparum and its mode of action. Overall, this study provides preliminary insights into P. falciparum malaria pathogenesis.<\/jats:p>","DOI":"10.1093\/bbb\/zbae209","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T02:22:06Z","timestamp":1736302926000},"page":"548-561","source":"Crossref","is-referenced-by-count":0,"title":["<i>Plasmodium falciparum<\/i> histidine-rich protein 2 exhibits cell penetration and cytotoxicity with autophagy dysfunction"],"prefix":"10.1093","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7119-1743","authenticated-orcid":false,"given":"Takashi","family":"Iwasaki","sequence":"first","affiliation":[{"name":"Department of Bioresource Science, Faculty of Agriculture, Tottori University , Tottori ,","place":["Japan"]},{"name":"Department of Agriculture, Graduate School of Sustainability Science, Tottori University , Tottori 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