Melatonin activates FIS1, DYN1 and DYN2 from Plasmodium falciparum genes related to mitochondrial fission: mitoemerald-GFP as a tool to visualize the structure of mitochondria

Malaria causes millions of deaths worldwide and is considered a huge burden for underdeveloped countries. The number of cases with resistance to all antimalarials is steadily increasing, making the identification of new drugs an urgent need. An interesting target for a new therapeutic intervention is the parasite’s mitochondria. This project studied the expression of genes that have broad sequence homology and/or structural homology with mammalian homologs, called FIS1, DYN1 and DYN2. Proteins are characterized by a distinct pattern of expression throughout the erythrocytic cycle of Plasmodium falciparum and their mRNAs are modulated by treating the parasite with the host hormone melatonin. It was previously reported that the elimination of the gene encoding protein kinase 7 is essential for the detection of melatonin. It was shown that here that the PfPk7 knockout results in major changes in the expression of mitochondrial fission genes when compared to wild type parasites, and no change in the expression of fission protein in treatment with the host hormone. Finally, the study compared the morphological characteristics (using a new GFP construct located in the mitochondrial matrix) and the oxygen consumption properties of the mitochondria of P. falciparum in wild type parasites and knockout strains for PfPk7. It is shown here that the functional characteristics of P. falciparum are profoundly altered in cells lacking protein kinase 7, suggesting that this enzyme plays an important role in the control of mitochondrial morphogenesis and maturation during the progression of the intra-erythrocyte cell cycle.

Project Details

Basic Science

Jul 2018 — Dec 2018

Brazil