%0 Journal Article
%A Pietsch, Emma
%A Ramaprasad, Abhinay
%A Bielfeld, Sabrina
%A Wohlfarter, Yvonne
%A Maco, Bohumil
%A Niedermüller, Korbinian
%A Wilcke, Louisa
%A Kloehn, Joachim
%A Keller, Markus A.
%A Soldati-Favre, Dominique
%A Blackman, Michael J.
%A Gilberger, Tim
%A Burda, Paul-Christian
%T A patatin-like phospholipase is important for mitochondrial function in malaria parasites
%J mBio
%V 14
%N 6
%@ 2161-2129
%C Washington, DC
%I American Society for Microbiology
%M PUBDB-2024-00239
%P e01718-23
%D 2023
%X 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. IMPORTANCEFor 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37882543
%U <Go to ISI:>//WOS:001097081100001
%R 10.1128/mbio.01718-23
%U https://bib-pubdb1.desy.de/record/601530