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Scientific article
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English

A patatin-like phospholipase is important for mitochondrial function in malaria parasites

Published inMBio, e0171823
Publication date2023-10-26
First online date2023-10-26
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 ( Pf PNPLA2, PF3D7_1358000) to the mitochondrion and reveal that disruption of the Pf PNPLA2 gene impairs asexual replication. Pf PNPLA2-null parasites are hypersensitive to proguanil and inhibitors of the mitochondrial ETC, including atovaquone. In addition, Pf PNPLA2-deficient parasites show reduced mitochondrial respiration and reduced mitochondrial membrane potential, indicating that disruption of Pf PNPLA2 leads to a defect in the parasite ETC. Lipidomic analysis of the mitochondrial phospholipid cardiolipin (CL) reveals that loss of Pf PNPLA2 is associated with a moderate shift toward shorter-chained and more saturated CL species, implying a contribution of Pf PNPLA2 to CL remodeling. Pf PNPLA2-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, Pf PNPLA2, as important for parasite replication and mitochondrial function in Plasmodium falciparum . Parasites lacking Pf PNPLA2 show defects in their ETC and become hypersensitive to mitochondrion-targeting drugs. Furthermore, Pf PNPLA2-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 Pf PNPLA2 have a defect in gametocyte maturation, underlining the importance of a functional ETC for parasite transmission to the mosquito vector.

eng
Keywords
  • Cardiolipin
  • Electron transport chain
  • Malaria
  • Mitochondrion
  • Patatin-like phospholipase
Funding
  • European Commission - Molecular Basis of Toxoplasma gondii Encystation and Persistence [695596]
Citation (ISO format)
PIETSCH, Emma et al. A patatin-like phospholipase is important for mitochondrial function in malaria parasites. In: MBio, 2023, p. e0171823. doi: 10.1128/mbio.01718-23
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Article (Published version)
Identifiers
ISSN of the journal2150-7511
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Technical informations

Creation10/30/2023 7:02:19 AM
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