TY  - JOUR
AU  - Pietsch, Emma
AU  - Ramaprasad, Abhinay
AU  - Bielfeld, Sabrina
AU  - Wohlfarter, Yvonne
AU  - Maco, Bohumil
AU  - Niedermüller, Korbinian
AU  - Wilcke, Louisa
AU  - Kloehn, Joachim
AU  - Keller, Markus A.
AU  - Soldati-Favre, Dominique
AU  - Blackman, Michael J.
AU  - Gilberger, Tim
AU  - Burda, Paul-Christian
TI  - A patatin-like phospholipase is important for mitochondrial function in malaria parasites
JO  - mBio
VL  - 14
IS  - 6
SN  - 2161-2129
CY  - Washington, DC
PB  - American Society for Microbiology
M1  - PUBDB-2024-00239
SP  - e01718-23
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37882543
UR  - <Go to ISI:>//WOS:001097081100001
DO  - DOI:10.1128/mbio.01718-23
UR  - https://bib-pubdb1.desy.de/record/601530
ER  -