Pietsch, Emma; Ramaprasad, Abhinay; Bielfeld, Sabrina; Wohlfarter, Yvonne; Maco, Bohumil; Niedermüller, Korbinian; Wilcke, Louisa; Kloehn, Joachim; Keller, Markus A; Soldati-Favre, Dominique; +3 more... Blackman, Michael J; Gilberger, Tim-Wolf; Burda, Paul-Christian; (2023) A patatin-like phospholipase is important for mitochondrial function in malaria parasites. mBio, 14 (6). e0171823. ISSN 2150-7511 DOI: https://doi.org/10.1128/mbio.01718-23
Permanent Identifier
Use this Digital Object Identifier when citing or linking to this resource.
Abstract
Plasmodium parasites rely on a functional electron transport chain (ETC) within their mitochondrion for proliferation, and compounds targeting mitochondrial functions are validated antimalarials. Here, we localize Plasmodium falciparum patatin-like phospholipase 2 (PfPNPLA2, PF3D7_1358000) to the mitochondrion and reveal that disruption of the PfPNPLA2 gene impairs asexual replication. PfPNPLA2-null parasites are hypersensitive to proguanil and inhibitors of the mitochondrial ETC, including atovaquone. In addition, PfPNPLA2-deficient parasites show reduced mitochondrial respiration and reduced mitochondrial membrane potential, indicating that disruption of PfPNPLA2 leads to a defect in the parasite ETC. Lipidomic analysis of the mitochondrial phospholipid cardiolipin (CL) reveals that loss of PfPNPLA2 is associated with a moderate shift toward shorter-chained and more saturated CL species, implying a contribution of PfPNPLA2 to CL remodeling. PfPNPLA2-deficient parasites display profound defects in gametocytogenesis, underlining the importance of a functional mitochondrial ETC during both the asexual and sexual development of the parasite. IMPORTANCE For their proliferation within red blood cells, malaria parasites depend on a functional electron transport chain (ETC) within their mitochondrion, which is the target of several antimalarial drugs. Here, we have used gene disruption to identify a patatin-like phospholipase, PfPNPLA2, as important for parasite replication and mitochondrial function in Plasmodium falciparum. Parasites lacking PfPNPLA2 show defects in their ETC and become hypersensitive to mitochondrion-targeting drugs. Furthermore, PfPNPLA2-deficient parasites show differences in the composition of their cardiolipins, a unique class of phospholipids with key roles in mitochondrial functions. Finally, we demonstrate that parasites devoid of PfPNPLA2 have a defect in gametocyte maturation, underlining the importance of a functional ETC for parasite transmission to the mosquito vector.
Item Type | Article |
---|---|
Faculty and Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology |
PubMed ID | 37882543 |
Elements ID | 210577 |
Official URL | http://dx.doi.org/10.1128/mbio.01718-23 |
Download
Filename: Pietsch-etal-2023-Patatin-like-phospholipase-is-important-for-mitochondrial-function-in-malaria-parasites.pdf
Licence: Creative Commons: Attribution 4.0
Download