Sabrina Absalon, PhD
Image credits: Indiana University
A newly characterized protein, dubbed PfAnchor, is essential for the division and inheritance of a vital organelle in Plasmodium falciparum, the deadliest malaria parasite. The discovery, published as a preprint on bioRxiv, could open the door to novel antimalarial strategies targeting parasite-specific processes.
The apicoplast, a non-photosynthetic plastid unique to Apicomplexan parasites, is required for parasite survival during the blood stage of infection. Because it cannot be created de novo, the apicoplast must be accurately divided and inherited during parasite replication. Disrupting this process leads to parasite death.
Researchers led by Sabrina Absalon, PhD, assistant professor of pharmacology and toxicology and assistant professor of microbiology and immunology at Indiana University School of Medicine, identified PfAnchor as the first known adaptor protein that enables apicoplast fission in malaria parasites. When PfAnchor was depleted, parasites failed to complete both apicoplast division and cytokinesis, resulting in rapid death within a single replication cycle.
“We originally found PfAnchor during a proximity labeling screen for proteins involved in nuclear division,” Absalon said. “But what really caught our attention was that it localized to the apicoplast and had a predicted pleckstrin homology domain—suggesting membrane association. Even more striking was that it has no homologs outside of Plasmodium, which often hints at a specialized and essential function.”
Using Ultrastructure Expansion Microscopy (U-ExM), the team visualized PfAnchor’s localization to the apicoplast throughout the parasite’s asexual blood-stage development. The study also demonstrated that PfAnchor physically interacts with PfDyn2, a dynamin-related GTPase responsible for membrane fission, positioning PfAnchor as a critical recruiter in the fission process.
“PfAnchor seems to help PfDyn2 find the apicoplast membrane at just the right time, similar to how dynamin adaptors work in other systems,” Absalon noted. “We also saw interactions with actin and chaperones, suggesting a broader network of proteins working together to manage organelle inheritance.”
In a surprising twist, the antibiotic azithromycin, known to disrupt apicoplast protein synthesis, was able to rescue the lethal phenotype caused by PfAnchor loss. Azithromycin collapses the apicoplast’s branched structure into small vesicles, which in turn allows the parasite to complete cytokinesis.
What You Need To Know
Investigators identified PfAnchor as a protein essential for the fission and inheritance of the apicoplast in Plasmodium falciparum.
The study suggests that targeting PfAnchor or apicoplast fission may provide a new approach for antimalarial drug development.
The research also found that PfAnchor interacts with PfDyn2 and other proteins, indicating a network involved in apicoplast division.
“We think the branched apicoplast normally tethers daughter parasites together, so without fission, they can’t separate,” Absalon explained. “Azithromycin’s ability to simplify that structure indirectly lets them finish dividing. This doesn’t mean azithromycin is a cure, but it highlights a new vulnerability. If we can disrupt apicoplast morphology or fission—potentially even with existing drugs—we may be able to kill parasites quickly, in just one replication cycle.”
Moving forward, the team plans to map the larger protein complex involved in organelle division. “We’re just scratching the surface. We think there’s an entire network coordinating fission with cytoskeletal remodeling,” Absalon added.
The findings underscore a promising avenue for antimalarial drug development by targeting parasite-specific mechanisms of organelle inheritance, a process vital to the pathogen’s survival yet absent in human cells.
Stay tuned for our video interview on World Malaria Day, April 25th, with Absalon, where we get into further detail and discuss how this discovery about PfAnchor helps in that bigger picture, maybe even helps lead to new treatments.
