⮝ Full datasets listing
PXD074429
PXD074429 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | A PROPPIN links V-ATPase assembly to endocytic membrane dynamics in malaria parasites |
| Description | Malaria 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. |
| HostingRepository | jPOST |
| AnnounceDate | 2026-07-24 |
| AnnouncementXML | Submission_2026-07-24_02:11:18.537.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Tanja Ziesmann |
| SpeciesList | scientific name: Plasmodium falciparum; NCBI TaxID: 5833; |
| ModificationList | S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide |
| Instrument | timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-02-13 05:35:19 | ID requested | |
| ⏵ 1 | 2026-07-24 02:11:19 | announced |
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 affiliation | Insitute of Immunology, University Medical Center Mainz |
| dataset submitter | |
Full Dataset Link List
| jPOST dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST004302/ |
