Melatonin activates FIS1, DYN1, and DYN2 Plasmodium falciparum related-genes for mitochondria fission: Mitoemerald-GFP as a tool to visualize mitochondria structure

Author(s):Show less -

Scarpelli, Pedro H. ^{[1, 2]} ; Tessarin-Almeida, Giulliana ^[2] ; Vicoso, Kenia Lopes ^[2] ; Lima, Wania Rezende ^[3] ; Borges-Pereira, Lucas ^[2] ; Meissner, Kamila Anna ^[1] ; Wrenger, Carsten ^[1] ; Rafaello, Anna ^[4] ; Rizzuto, Rosario ^[4] ; Pozzan, Tullio ^[4] ; Garcia, Celia R. S. ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, Sao Paulo - Brazil

^[3] Univ Fed Mato Grosso, Inst Ciencias Exatas & Nat Med, Campus Rondonopolis, Cuiaba, Mato Grosso - Brazil

^[4] Univ Padua, CNR Neurosci Inst, Padua - Italy

• Document type: Review article
• Source: Journal of Pineal Research; v. 66, n. 2 MAR 2019.
• Web of Science Citations: 4

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 Plasmodium falciparum 3 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 P. falciparum, and their mRNAs 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 PfPk7 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 PfPk7 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. (AU)

• FAPESP's process: 12/12807-3 - Analysis of the redox status and its effect on the proliferation of Plasmodium falciparum in genetically different erythrocytes
• Grantee: Kamila Anna Meissner
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/51295-5 - Functional genomics in Plasmodium
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/14347-5 - Dissect signalling pathways in Plasmodium-host interaction: role of PfNF-YB transcription fator
• Grantee: Pedro Henrique Scarpelli Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
• Grantee: Carsten Wrenger
• Support Opportunities: Research Projects - Thematic Grants