# An Essential Adaptor for Apicoplast Fission and Inheritance in Malaria Parasites

**Authors:** James Blauwkamp, Krithika Rajaram, Sophia R. Staggers, Oliver Harrigan, Emma H. Doud, Sean T. Prigge, Stella Y. Sun, Sabrina Absalon

PMC · DOI: 10.21203/rs.3.rs-6457426/v1 · Research Square · 2025-05-05

## TL;DR

Researchers discovered a protein called PfAnchor that is crucial for the division and inheritance of the apicoplast in malaria parasites, offering a new target for antimalarial drugs.

## Contribution

Identification of PfAnchor as the first apicoplast-specific dynamin adaptor protein regulating apicoplast fission in Plasmodium falciparum.

## Key findings

- PfAnchor localizes to the apicoplast and is essential for its fission during parasite cell division.
- Conditional depletion of PfAnchor disrupts apicoplast fission and leads to parasite death.
- PfAnchor interacts with PfDyn2, a key mediator of organelle fission, establishing its role as a dynamin adaptor.

## Abstract

Blood-stage Plasmodium falciparum parasites rely on a non-photosynthetic plastid, the apicoplast, for survival, making it an attractive target for antimalarial intervention. Like the mitochondrion, the apicoplast cannot be generated de novo and must be inherited by daughter parasites during cell division. This inheritance relies on coordinated apicoplast positioning and fission, but the molecular mechanisms controlling these processes remain poorly understood. Here, we identify a previously uncharacterized P. falciparum protein (Pf3D7_0613600), which we name PfAnchor, as a key regulator of apicoplast fission. Using Ultrastructure Expansion Microscopy (U-ExM), we show that PfAnchor localizes to the apicoplast throughout the asexual blood-stage. Conditional depletion disrupts apicoplast fission, leading to incomplete cytokinesis and parasite death. Notably, loss of the apicoplast’s elongated branched structure via azithromycin treatment rescues these defects, underscoring Anchor’s specific role in apicoplast fission. Immunoprecipitation identified an interaction with the dynamin-like GTPase PfDyn2, a key mediator of both apicoplast and mitochondrial fission, establishing PfAnchor as the first apicoplast-specific dynamin adaptor protein. Our findings define PfAnchor as an essential factor for apicoplast fission and inheritance in P. falciparum blood-stage parasites, highlighting parasite-specific organelle division as a potential vulnerability for therapeutic intervention.

## Linked entities

- **Genes:** PF3D7_0613600 (conserved Plasmodium protein, unknown function) [NCBI Gene 3885758]
- **Chemicals:** azithromycin (PubChem CID 447043)
- **Diseases:** malaria (MONDO:0005136)
- **Species:** Plasmodium falciparum (taxon 5833)

## Full-text entities

- **Diseases:** Apicoplast Fission (OMIM:614388), Malaria Parasites (MESH:D008288)
- **Chemicals:** azithromycin (MESH:D017963)
- **Species:** Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12083691/full.md

## References

78 references — full list in the complete paper: https://tomesphere.com/paper/PMC12083691/full.md

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Source: https://tomesphere.com/paper/PMC12083691