Scarpelli 2018 J Pineal Res
|Scarpelli P, Almeida GT, Viçoso KL, Lima WR, Pereira LB, Meissner KA, Wrenger C, Rafaello A, Rizzuto R, Pozzan T, Garcia CRS (2018) Melatonin activate FIS1, DYN1 and DYN2 Plasmodium falciparum related-genes for mitochondria fission: mitoemerald-GFP as a tool to visualize mitochondria structure. J Pineal Res [Epub ahead of print].|
Abstract: Malaria causes millions of deaths worldwide and is considered a huge burden to underdeveloped countries. The number of cases with resistance to all antimalarials is continuously increasing, making the identification of novel drugs a very urgent necessity. A potentially very interesting target for novel therapeutic intervention is the parasite mitochondrion. In this work we studied in P. falciparum three genes coding for proteins homologues of the mammalian FIS1 (Mitochondrial Fission Protein 1) and DRP1 (Dynamin Related Protein 1) involved in mitochondrial fission. We studied the expression of P. falciparum genes that show ample sequence and structural homologies with the mammalian counterparts, namely FIS1, DYN1 and DYN2. The encoded 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. We have previously reported that the knock out of the Plasmodium gene that codes for protein kinase 7 is essential for melatonin sensing. We here show that PfPk7 knockout results in major alterations of mitochondrial fission genes expression when compared to wild type parasites, and no change in fission protein expression upon treatment with the host hormone. Finally we have compared the morphological characteristics(using MitoTracker Red CMX Ros. and oxygen consumption properties of P. falciparum mitochondria in wild type parasites and PfPk7 Knockout strains. A novel GFP construct targeted to the mitochondrial matrix to wild type parasites was also developed to visualize Plasmodium falciparum mitochondria. We here show that, the functional characteristics of P. falciparum are profoundly altered in cells lacking protein kinase 7, suggesting that this enzyme plays a major role in the control of mitochondrial morphogenesis and maturation during the intra erythrocyte cell cycle progression. This article is protected by copyright. All rights reserved.
• Bioblast editor: Kandolf G
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression, Pharmacology;toxicology
Preparation: Intact organism
Coupling state: LEAK, ROUTINE, ET