Biology subjects

Söhnchen, C.

Publications and source records attributed to Söhnchen, C..

2 recordsLinked to original sources

bioRxiv2021

Global analysis of putative phospholipases in the malaria parasite Plasmodium falciparum reveals critical factors for parasite proliferation

For its replication within red blood cells, the malaria parasite is highly dependent on correctly regulated lipid metabolism. Enzymes involved in lipid metabolic processes are therefore potential drug targets. We here provide a functional analysis of the 20 putative phospholipases that are expressed by asexual blood stages of Plasmodium falciparum. We reveal a high level of redundancy among members of this group, but using conditional mislocalization and gene disruption techniques we show that the phosphoinositide-specific phospholipase C (PF3D7_1013500) has a previously unrecognized essential role in intracellular parasite maturation. In addition, we demonstrate that the patatin-like phospholipase PF3D7_1358000 localizes to the mitochondrion. Parasites lacking this enzyme display a severe growth phenotype and defects in mitochondrial morphogenesis and function leading to hypersensitivity towards proguanil and inhibitors of the mitochondrial electron transport chain including atovaquone. This demonstrates that regulated mitochondrial lipid homeostasis is necessary for mitochondrial function and coordinated division during parasite multiplication.

microbiology↗

bioRxiv2020

Structure-based identification and functional characterization of an essential lipocalin in the malaria parasite Plasmodium falciparum

Proteins of the lipocalin family are known to bind small hydrophobic ligands and are involved in various physiological processes ranging from lipid transport to oxidative stress responses. The genome of the malaria parasite Plasmodium falciparum contains a single protein PF3D7_0925900 with a lipocalin signature. Using crystallography and small-angle X-ray scattering, we show that the protein has a tetrameric structure of typical lipocalin monomers, hence we name it P. falciparum lipocalin (PfLCN), the first lipocalin structurally and functionally characterized in a single-celled eukaryote. We show that PfLCN is expressed in the intraerythrocytic stages of the parasite and localizes to the parasitophorous and food vacuoles. Conditional knockdown of PfLCN impairs parasite development, which can be rescued by treatment with the radical scavenger Trolox or by temporal inhibition of hemoglobin digestion. This suggests a key function of PfLCN in counteracting oxidative stress induced cell damage during multiplication of parasites within red blood cells.

cell biology↗