Apicoplast Dynamics During Plasmodium Cell Cycle

Abstract

The deadly malaria parasite, Plasmodium falciparum, contains a unique subcellular organelle termed the apicoplast, which is a clinically-proven antimalarial drug target. The apicoplast is a plastid with essential metabolic functions that evolved via secondary endosymbiosis. As an ancient endosymbiont, the apicoplast retained its own genome and it must be inherited by daughter cells during cell division. During the asexual replication of P. falciparum inside human red blood cells, both the parasite, and the apicoplast inside it, undergo massive morphological changes, including DNA replication and division. The apicoplast is an integral part of the cell and thus its development is tightly synchronized with the cell cycle. At the same time, certain aspects of its dynamics are independent of nuclear division, representing a degree of autonomy in organelle biogenesis. Here, we review the different aspects of organelle dynamics during P. falciparum intraerythrocytic replication, summarize our current understanding of these processes, and describe the many open questions in this area of parasite basic cell biology.

Keywords: apicoplast; cell cycle; malaria; organelle dynamics; plasmodium; schizogony.

Figure 1

Apicoplast dynamics during intraerythrocytic development of Plasmodium falciparum. (A) Schematic representation of apicoplast dynamics during intraerythrocytic asexual replication of P. falciparum. RBC, red blood cell; PV, parasitophorous vacuole; IMC, inner membrane complex, PM, plasma membrane Created with BioRender.com. (B) Fluorescent microcopy of live apicoplast-tagged parasites (ACP-DsRed) co-labelled with a nuclear Hoechst dye. Apicoplast morphology was categorized into four groups based on developmental stage: (i) rounded (ii) elongated (iii) branched and (iv) divided. Image taken from van Dooren et al. (2005). (C). Apicoplast morphologies throughout segmentation. By mid-segmentation, apicoplasts have divided to form one organelle for each nascent daughter cell. Ultra-resolution images were obtained using FIB-SEM, taken from Rudlaff et al. (2020).