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PXD074429-1

PXD074429 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA PROPPIN links V-ATPase assembly to endocytic membrane dynamics in malaria parasites
DescriptionMalaria parasites replicate inside red blood cells, degrading hemoglobin within a specialized digestive vacuole. Efficient hemoglobin processing is essential for parasite survival and influences antimalarial drug susceptibility. The vacuole constantly fuses with incoming hemoglobin-filled vesicles, yet the mechanisms that balance cargo influx with membrane homeostasis remain unclear. Here, using conditional reverse genetics, quantitative live-cell imaging, and 3D electron microscopy, we characterize the autophagy-related protein 18 of Plasmodium falciparum (PfATG18) as a key regulator of vacuolar membrane dynamics. Loss of PfATG18 caused vacuole fragmentation, accumulation of hemoglobin-filled vesicles, and parasite death. These defects were preceded by broad architectural destabilization of the parasite’s V-ATPase, a proton pump controlling organelle acidification and the vacuole’s fusion–fission equilibrium. Direct interference with its membrane sector phenocopied PfATG18 deficiency. We found that PfATG18 does not interact directly with the proton pump but instead associates with a putative V-ATPase assembly factor and with complexes regulating phosphoinositide balance and vesicle trafficking. The breadth of these interactions indicates a multifaceted role at the vacuolar membrane and a regulatory influence on V-ATPase mediated through associated protein machinery. Although a point mutation in PfATG18 has been linked to artemisinin resistance, its complete knockout did not decrease sensitivity, but rather hypersensitized ring-stage parasites to dihydroartemisinin. Together, these findings establish PfATG18 as a central regulator of endocytic membrane homeostasis, essential for V-ATPase function and asexual parasite proliferation in the human blood.
HostingRepositoryjPOST
AnnounceDate2026-07-24
AnnouncementXMLSubmission_2026-07-24_02:11:18.537.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTanja Ziesmann
SpeciesList scientific name: Plasmodium falciparum; NCBI TaxID: 5833;
ModificationListS-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-02-13 05:35:19ID requested
12026-07-24 02:11:19announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Malaria, Plasmodium, ATG18, autophagy, vacuole, fusion, fission, V-ATPase, endocytosis
Contact List
Joachim Michael Matz
lab head
Tanja Ziesmann
contact affiliationInsitute of Immunology, University Medical Center Mainz
dataset submitter
Full Dataset Link List
jPOST dataset URI
Dataset FTP location
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