A cytoskeleton-associated Plasmodium protein critical for organelle segregation

Abstract

The malaria parasite, Plasmodium falciparum, replicates asexually within red blood cells by schizogony, a mode of division in which organelles divide multiple times before a final coordinated cytokinesis event, called segmentation, partitions them into dozens of merozoites. The Plasmodium cytoskeleton functions critically during this process, facilitating one-per-cell organelle segregation. Here, we identify and characterize a cytoskeleton-associated protein, PfOGRE (organelle retention, PF3D7_1435600), required for segregation of the mitochondrion and apicoplast, a non-photosynthetic plastid. Immunofluorescence paired with ultrastructure expansion microscopy demonstrates that PfOGRE localizes alongside subpellicular microtubules in nascent merozoites, adjacent to the segregating apicoplast. Conditional knockout of PfOGRE produces organelle-less merozoites with abnormal subpellicular microtubules, impairing asexual replication. Immunoprecipitation and mass spectrometry identify several candidate interactors, including PfMyoF. Conditional knockdown of PfMyoF produces similar organelle segregation defects. Together, these results establish PfOGRE as a critical mediator of organelle segregation and define a non-structural role for Plasmodium subpellicular microtubules during this process. The Plasmodium cytoskeleton is critical for parasite replication. Here, Navarro et al identify and characterise a cytoskeleton-associated protein required for organelle segregation and asexual replication.