Journal article
The dynamin-related protein PfDyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum
mBio, pe0303624
29 Nov 2024
PMID: 39611847
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Dynamins, or dynamin-related proteins (DRPs), are large mechano-sensitive GTPases that mediate membrane dynamics or organellar fission/fusion events.
encodes three dynamin-like proteins whose functions are poorly understood. Here, we demonstrate that one of these dynamin-related proteins, PfDyn2, is required to divide both the apicoplast and the mitochondrion, a striking divergence from the biology of related parasites. Using super-resolution and ultrastructure expansion microscopy (U-ExM), we show that PfDyn2 is expressed in dividing schizonts, and that it localizes to both the apicoplast and the mitochondrion. Our use of long-term, live-cell microscopy allows for the visualization of apicoplast and mitochondrial division in live parasites at super resolution for the first time, and demonstrates that in PfDyn2-deficient parasites, while the apicoplast and mitochondrion increase in size and complexity, they do not undergo fission. We also show that these organellar fission defects prevent successful individualization of the schizont mass and the formation of new daughter cells, or merozoites because the basal complex, the cytokinetic ring of
, cannot fully contract in PfDyn2-deficient parasites, a phenotype secondary to physical blockage by undivided organelles occluding the ring. PfDyn2's singular role in mediating both apicoplast and mitochondrial fission has not been observed in other organisms possessing two endosymbiotic organelles, including other Apicomplexans, thus reflecting a unique, potentially exploitable method of organellar division in
.IMPORTANCE
remains a significant global pathogen, causing over 200 million infections and over 600,000 deaths per year. One significant obstacle to the control of malaria is increasing resistance to first-line artemisinin-based antimalarials. Another is a lack of basic knowledge about the cell biology of the parasite. Along with the mitochondrion,
contains a second organelle descended from an endosymbiotic event, the apicoplast. Both organelles are common targets for antimalarials, but because many proteins involved in organellar fission are not conserved in
, until now, the mechanisms underlying apicoplast and mitochondrial division have been unknown. In this study, we demonstrate that PfDyn2, a dynamin-related protein (DRP), is required for the division of both organelles. We also show that defects in organellar division hinder segmentation of the schizont and formation of invasive merozoites by preventing full contraction of the basal complex. By demonstrating its necessity for the proper division of both the apicoplast and the mitochondria, this study highlights PfDyn2 as a potential target for new antimalarials.
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Details
- Title
- The dynamin-related protein PfDyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum
- Creators
- Alexander A Morano - Boston Children's HospitalWei Xu - Drexel UniversityFrancesca M Navarro - Boston Children's HospitalNeeta Shadija - Drexel UniversityJeffrey D Dvorin - Boston Children's HospitalHangjun Ke - Drexel University
- Publication Details
- mBio, pe0303624
- Publisher
- AMER SOC MICROBIOLOGY; WASHINGTON
- Number of pages
- 23
- Grant note
- HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
We thank Sean Prigge for providing the rabbit anti-PfACP antisera, Scott Lindner for providing the rabbit anti-PyACP antisera, Julian Rayner for providing the rabbit anti-PfGAP45 antisera, Anthony Holder for providing the mouse anti-PfMSP1 antibody, and Joshua Beck for providing the NF54attB line. We are grateful to the former members of the Ke laboratory, Dr. Liqin Ling, Rachel Reviello, Dr. Mulaka Maruthi, Dr. Swati Dass, in helping us make plasmid constructs; to Ikechukwu Nwankwo for technical assistance; and to members of the Center for Parasitology at Drexel University College of Medicine for helpful discussions.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001367237300001
- Scopus ID
- 2-s2.0-85214326999
- Other Identifier
- 991021969000904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology