Melatonin activates FIS 1, DYN 1, and DYN 2 Plasmodium falciparum related‐genes for mitochondria fission: Mitoemerald‐ GFP as a tool to visualize mitochondria structure

• Published in: Journal of pineal research Vol. 66; no. 2
• Main Authors: Scarpelli, Pedro H., Tessarin‐Almeida, Giulliana, Viçoso, Kênia Lopes, Lima, Wania Rezende, Borges‐Pereira, Lucas, Meissner, Kamila Anna, Wrenger, Carsten, Raffaello, Anna, Rizzuto, Rosario, Pozzan, Tullio, Garcia, Celia R. S.
• Format: Journal Article
• Language: English
• Published: 01-03-2019
• ISSN: 0742-3098; 1600-079X
• DOI: 10.1111/jpi.12484

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
Plasmodium falciparum
3 genes coding for proteins homologues of the mammalian
FIS
1 (Mitochondrial Fission Protein 1) and
DRP
1 (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
FIS
1,
DYN
1, and
DYN
2. The encoded proteins are characterized by a distinct pattern of expression throughout the erythrocytic cycle of
P. falciparum,
and their
mRNA
s are modulated by treating the parasite with the host hormone melatonin. We have previously reported that the knockout of the
Plasmodium
gene that codes for protein kinase 7 is essential for melatonin sensing. We here show that
Pf
Pk7 knockout results in major alterations of mitochondrial fission genes expression when compared to wild‐type parasites, and no change in fission proteins 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
Pf
Pk7 Knockout strains. A novel
GFP
construct targeted to the mitochondrial matrix to wild‐type parasites was also developed to visualize
P. 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.