Journal Article

Comparative 3D ultrastructure of Plasmodium falciparum gametocytes

Verhoef, Julie M. J., Sommerdijk, Nico, Boshoven, Cas, Sinden, Robert E., Kooij, Taco W. A., Roverts, Rona, Kea-te Lindert, Mariska, Akiva, Anat, Evers, Felix

2025

Overview

Despite the enormous significance of malaria parasites for global health, some basic features of their ultrastructure remain obscure. Here, we apply high-resolution volumetric electron microscopy to examine and compare the ultrastructure of the transmissible male and female sexual blood stages of Plasmodium falciparum as well as the more intensively studied asexual blood stages revisiting previously described phenomena in 3D. In doing so, we challenge the widely accepted notion of a single mitochondrion by demonstrating the presence of multiple mitochondria in gametocytes. We also provide evidence for a gametocyte-specific cytostome, or cell mouth. Furthermore, we generate the first 3D reconstructions of the parasite’s endoplasmic reticulum (ER) and Golgi apparatus as well as gametocyte-induced extraparasitic structures in the infected red blood cell. Assessing interconnectivity between organelles, we find frequent structural appositions between the nucleus, mitochondria, and apicoplast. We provide evidence that the ER is a promiscuous interactor with numerous organelles and the trilaminar pellicle of the gametocyte. Public availability of these volumetric electron microscopy resources will facilitate reinterrogation by others with different research questions and expertise. Taken together, we reconstruct the 3D ultrastructure of P. falciparum gametocytes at nanometre scale and shed light on the unique organellar biology of these deadly parasites. Evers et al. generated exceptionally detailed 3D reconstructions of different malaria parasite stages responsible for pathology and spread of the disease. The nanometre scale ultrastructures shed light on the unique cell biology of these deadly parasites.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/28 / 631/326/417/1716 / 631/326/421 / 631/80/642 / Biology / Blood / Blood parasites / Electron microscopy / Endoplasmic reticulum / Endoplasmic Reticulum - ultrastructure / Erythrocytes / Erythrocytes - parasitology / Erythrocytes - ultrastructure / Female / Gametocytes / Germ Cells - ultrastructure / Global health / Golgi Apparatus - metabolism / Golgi Apparatus - ultrastructure / Golgi cells / Humanities and Social Sciences / Humans / Imaging, Three-Dimensional / Malaria / Malaria, Falciparum - parasitology / Male / Microscopy / Microscopy, Electron / Mitochondria / Mitochondria - ultrastructure / multidisciplinary / Organelles / Organelles - ultrastructure / Parasites / Pellicle / Plasmodium falciparum / Plasmodium falciparum - ultrastructure / Public health / Science / Science (multidisciplinary) / Ultrastructure / Vector-borne diseases