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Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) the Erythrocytic Development of Plasmodium falciparum
Journal article   Open access   Peer reviewed

Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) the Erythrocytic Development of Plasmodium falciparum

Mulaka Maruthi, Liqin Ling, Jing Zhou and Hangjun Ke
mSphere, v 5(5)
01 Sep 2020
PMID: 32968006
url
https://doi.org/10.1128/msphere.00579-20View
Published, Version of Record (VoR)CC BY V4.0 Open
url
https://doi.org/10.1128/mSphere.00579-20View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Microbiology Science & Technology
Malaria remains a huge global health burden, and control of this disease has run into a severe bottleneck. To defeat malaria and reach the goal of eradication, a deep understanding of the parasite biology is urgently needed. The mitochondrion of the malaria parasite is essential throughout the parasite's life cycle and has been validated as a clinical drug target. In the asexual development of Plasmodium spp., the single mitochondrion grows from a small tubular structure to a complex branched network. This branched mitochondrion is divided at the end of schizogony when 8 to 32 daughter cells are produced, distributing one mitochondrion to each forming merozoite. In mosquito and liver stages, the giant mitochondria' network is split into thousands of pieces and daughter mitochondria are segregated into individual progeny. Despite the significance of mitochondria' fission in Plasmodium, the underlying mechanism is largely unknown. Studies of mitochondria' fission in model eukaryotes have revealed that several mitochondria' fission adaptor proteins are involved in recruiting dynamin GTPases to physically split mitochondria' membranes. Apicomplexan parasites, however, share no identifiable homologs of mitochondrial fission adaptor proteins with yeast or humans, except for Fis1. Here, we investigated the localization and essentiality of the Fis1 homolog in Plasmodium falciparum, PfFis1 (PF3D7_1325600), during the asexual life cycle. We found that PfFis1 requires an intact C terminus for mitochondria' localization but is not essential for parasite development or mitochondria' fission. The dispensable role of PfFis1 indicates that Plasmodium contains additional fission adaptor proteins on the mitochondria' outer membrane that could be essential for mitochondrial fission. IMPORTANCE Malaria is responsible for over 230 million clinical cases and similar to half a million deaths each year. The single mitochondrion of the malaria parasite functions as a metabolic hub throughout the parasite's developmental cycle (DC) and also as a source of ATP in certain stages. To pass on its essential functions, the parasite's mitochondrion needs to be properly divided and segregated into all progeny during cell division via a process termed mitochondrial fission. Due to the divergent nature of Plasmodium spp., the molecular players involved in mitochondria' fission and their mechanisms of action remain largely unknown. Here, we found that the only identifiable mitochondria' fission adaptor protein that is evolutionarily conserved in the Apicomplexan phylum, Fis1, it not essential in P. falciparum asexual stages. Our data suggest that malaria parasites use redundant fission adaptor proteins on the mitochondria' outer membrane to mediate the fission process.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Microbiology
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