Elucidation of the metabolic pathway of lipid peroxide in Plasmodium erythrophyllum

Malaria, one of the three major infectious diseases, is caused by human malaria parasites (Plasmodium erythrocytes) that infect erythrocytes. Akauchi-type malaria parasites must proliferate while being exposed to a high degree of oxidative stress due to active oxygen derived from hemoglobin taken in as nutrients and oxygen in the bloodstream. It has been revealed that lipid peroxides produced by reactive oxygen induce a decrease in the viscoelasticity of cell membranes, DNA damage, and iron-dependent cell death called ferroptosis. This suggests that a metabolic pathway for removing peroxidized lipids, which are harmful to the malaria parasite, is essential for its proliferation within red blood cells. However, the current situation is that the knowledge about the metabolic pathway of lipid peroxide in malaria parasites is overwhelmingly lacking compared to that of mammalian cells. By homology search by BLAST, the applicant identified a protozoan homologue of a protein involved in the lipid peroxide metabolic pathway of mammalian cells. Genetically modified protozoa are created by knocking out (KO) or conditionally knocking down (cKD) these genes. The amount of lipid peroxide in these strains is detected by fluorescent reagents or mass spectrometry using the genetically modified protozoa produced. This confirms that the gene functions in the lipid peroxide pathway. Finally, phenotypic analysis of genetically modified parasites will focus on ferroptosis markers to ascertain how lipid peroxide accumulation affects malaria parasites.

Project details

Basic Science

Apr 2021 — Mar 2025

$38,868

Japan