Authors:

Mercy Olaniyan

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About Paper:

Malaria, caused by Plasmodium falciparum, remains a major global health burden with over 234 million cases annually. (PMID: 40056919) Parasite survival depends on the apicoplast, a specialized organelle essential for growth and development. Proper inheritance of the apicoplast during cell division requires a dynamic actin cytoskeleton, yet the specific role of actin regulation in organelle segregation remains unclear. We hypothesized that disrupting actin dynamics would impair apicoplast and mitochondrial segregation during the parasite's asexual blood stage. To test this hypothesis, multinucleated NF54-Mev parasites were treated with two actin inhibitors: SZ-3, which blocks cofilin binding to filamentous actin and Cytochalasin D, which caps actin filament barbed ends (PMID: 33585284). Dimethylsulfoxide (DMSO) served as a negative control. Following drug treatment, parasites were analyzed using ultrastructure expansion microscopy to assess apicoplast and mitochondrial morphology and inheritance in developing merozoites. Control parasites displayed expected organelle remodeling prior to host cell rupture, with rounded apicoplasts and elongated mitochondria that properly segregated into daughter cells. (PMID: 34425697) In contrast, Cytochalasin D treatment disrupted organelle inheritance: although fission occurred, both the apicoplast and mitochondrion collapsed into the residual body and failed to segregate. SZ-3 treatment preserved apicoplast remodeling but altered mitochondrial morphology, producing a previously unobserved "mitochondrial looping" phenotype in which the mitochondrion tightly encircled the apicoplast. These findings demonstrate that actin dynamics are essential for proper organelle segregation in P. falciparum and reveal distinct roles for actin regulatory mechanisms in apicoplast and mitochondrial inheritance. This work advances understanding of parasite cell biology and highlights cytoskeletal regulation as a potential target for antimalarial strategies.

Source:

Northwestern University

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Co-authors:

Mercy Olaniyan