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bioRxiv · 10.1101/2020.06.18.160663

A dispensable role of mitochondrial fission protein 1 (Fis1) in the erythrocytic development of Plasmodium falciparum

Maruthi, M.·Ling, L.·Zhou, J.·Ke, H.
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Abstract

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 parasite biology is urgently needed. The mitochondrion of the malaria parasite is essential throughout the parasites lifecycle 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. At the end of schizogony when 8-32 merozoites are produced, the branched mitochondrion is precisely divided, distributing one mitochondrion to each forming daughter merozoite. In mosquito and liver stages, the giant mitochondrial network is split into thousands of pieces then daughter mitochondria are segregated into individual progeny. Despite the significance of mitochondrial fission in Plasmodium, the underlying mechanism is largely unknown. Studies of mitochondrial fission in model eukaryotes have revealed that several mitochondrial fission adaptor proteins are involved in recruiting dynamin GTPases to physically split mitochondrial membranes. Apicomplexan parasites, however, share no identifiable homologs of mitochondrial fission adaptor proteins of yeast or human, except for Fis1. Here, we investigated the localization and essentiality of the Fis1 homolog in Plasmodium falciparum, PfFis1 (PF3D7_1325600), during the asexual lifecycle. We found that PfFis1 requires an intact C-terminus for mitochondrial localization but is not essential for parasite development or mitochondrial fission. The dispensable role of PfFis1 indicates Plasmodium contains additional fission adaptor proteins on the mitochondrial outer membrane that could be essential for mitochondrial fission. ImportanceMalaria is responsible for over 230 million clinical cases and [~] half a million deaths each year. The single mitochondrion of the malaria parasite functions as a metabolic hub throughout the parasites developmental cycle as well as a source of ATP in certain stages. To pass on its essential functions, the parasites mitochondrion needs to be properly divided and segregated into all progeny during cell division via a process named mitochondrial fission. Due to the divergent nature of Plasmodium spp., molecular players involved in mitochondrial fission and their mechanisms of action remain largely unknown. We found that Fis1, the only identifiable mitochondrial fission adaptor protein evolutionarily conserved in the phylum of Apicomplexa, however, is not essential for Plasmodium falciparum. Our data suggest that malaria parasites use redundant fission adaptor proteins on the mitochondrial outer membrane to mediate the fission process.

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Maruthi, M., Ling, L., Zhou, J., Ke, H.. 2020-06-19. A dispensable role of mitochondrial fission protein 1 (Fis1) in the erythrocytic development of Plasmodium falciparum. https://doi.org/10.1101/2020.06.18.160663

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