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bioRxiv · 10.1101/2024.03.15.585229

The dynamin-related protein Dyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum

Abstract

Dynamins, or dynamin-related proteins (DRPs), are large mechano-sensitive GTPases mediating membrane dynamics or organellar fission/fusion events. Plasmodium falciparum encodes three dynamin-like proteins whose functions are poorly understood. Here, we demonstrate that PfDyn2 mediates both apicoplast and mitochondrial fission. Using super-resolution and ultrastructure expansion microscopy, we show that PfDyn2 is expressed in the schizont stage and localizes to both the apicoplast and mitochondria. Super-resolution long-term live cell microscopy shows that PfDyn2-deficient parasites cannot complete cytokinesis because the apicoplast and mitochondria do not undergo fission. Further, the basal complex or cytokinetic ring in Plasmodium cannot fully contract upon PfDyn2 depletion, a phenotype secondary to physical blockage of undivided organelles in the middle of the ring. Our data suggest that organellar fission defects result in aberrant schizogony, generating unsuccessful merozoites. The unique biology of PfDyn2, mediating both apicoplast and mitochondrial fission, has not been observed in other organisms possessing two endosymbiotic organelles. HighlightsO_LIPfDyn2 is essential for schizont-stage development. C_LIO_LIPfDyn2 mediates both apicoplast and mitochondrial fission. C_LIO_LIDeficiency of PfDyn2 leads to organellar fission failures and blockage of basal complex contraction. C_LIO_LIAddition of apicoplast-derived metabolite IPP does not rescue the growth defects. C_LI

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Morano, A. A., Xu, W., Shadija, N., Dvorin, J. D., Ke, H.. 2024-03-17. The dynamin-related protein Dyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum. https://doi.org/10.1101/2024.03.15.585229

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