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oai:figshare.com:article/34017851 2026-09-28T17:54:58Z category_1 category_4 category_915 category_7 category_8 category_12 category_13 category_132 portal_5 item_type_1 month_year_09_2026

<p>Loss of <i>Pf</i>ATG18 causes hemozoin dislocation and parasite death.</p> Yasmin Schmitz (11974910) Moumita Sengupta (25132859) Carola Schneider (3743791) Tanja Ziesmann (3318936) Franziska Hellmold (25132862) Ute Distler (115774) Rudolph Reimer (190562) Joachim Michael Matz (25132865) Biophysics Biochemistry Physical Sciences not elsewhere classified Medicine Microbiology Cell Biology Genetics Infectious Diseases related protein 18 div >< p broad architectural destabilization balance cargo influx associated protein machinery antimalarial drugs unchanged 3d electron microscopy membrane sector phenocopied endocytic membrane homeostasis endocytic membrane dynamics vacuole constantly fuses specialized digestive vacuole stage parasites hypersensitive vacuolar membrane dynamics efficient hemoglobin processing degrading hemoglobin within asexual parasite proliferation plasmodium falciparum </ atpase assembly factor atg18 links v vacuolar membrane vacuole ’ malaria parasites atpase assembly parasite ’ parasite survival parasite death incoming hemoglobin pf </ vesicle trafficking rendered ring regulatory influence quantitative live proton pump point mutation multifaceted role key regulator interactions indicates interact directly findings establish filled vesicles direct interference decrease sensitivity <p>Synchronized parasites were treated with DMSO or RAP from the ring stage onward. <b>(A)</b> RAP-induced excision of <i>loxP</i>-flanked genomic DNA in <i>atg18-mNG:loxP</i> parasites, confirmed by diagnostic PCR 5 (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1014608#ppat.1014608.g001" target="_blank">Figure 1A</a>). <b>(B-E)</b> RAP efficiently depletes <i>Pf</i>ATG18-mNG by 36 hours post invasion, as shown by Western blot <b>(B)</b> and live-cell imaging <b>(C)</b>. Quantitative fluorescence microscopy reveals strong reduction of <i>Pf</i>ATG18 <b>(D)</b>, but not CRT <b>(E)</b>, following RAP treatment. Parental B11 parasites [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1014608#ppat.1014608.ref043" target="_blank">43</a>] serve as background control. Mean + /- SD; one-way ANOVA with Tukey’s test; n = 99 parasites, 3 experiments. n.s., <i>p</i> > 0.05; ***, <i>p</i> < 0.001. <b>(F-H)</b> <i>Pf</i>ATG18 is essential for asexual blood-stage development. RAP blocks replication of <i>atg18-mNG:loxP</i> parasites <b>(F)</b> but not B11 controls <b>(G)</b>. Individual values; two-way ANOVA; n = 3 experiments with 3 technical replicates each. <b>(H)</b> Giemsa-stained <i>atg18-mNG:loxP</i> parasites throughout one intraerythrocytic cycle. <b>(I-K)</b> Loss of <i>Pf</i>ATG18 alters hemozoin distribution. <b>(I)</b> Giemsa-stained parasites imaged by brightfield and polarization microscopy. Hemozoin dispersal area <b>(J)</b> and parasite area <b>(K)</b> were quantified. Mean + /- SEM; two-way ANOVA; n = 99 parasites, 3 experiments. *, <i>p</i> < 0.05; **, <i>p</i> < 0.01. Scale bars: 5 µm. Source data are provided as a <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1014608#ppat.1014608.s015" target="_blank">S3 File</a>.</p> 2026-09-28T18:08:16Z Image Figure 10.1371/journal.ppat.1014608.g002 https://figshare.com/articles/figure/_p_Loss_of_i_Pf_i_ATG18_causes_hemozoin_dislocation_and_parasite_death_p_/34017851 CC BY 4.0