Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling

Abstract

Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan, largely contain disease-causing parasites and characterized by the presence of apicoplast. It is a very essential organelle of P. falciparum responsible for the synthesis of key molecules required for the growth of the parasite. Indispensable nature of apicoplast makes it a potential drug target. Calcium signaling is important in the establishment of malaria parasite inside the host. It has been involved in invasion and egress of merozoites during the asexual life cycle of the parasite. Calcium signaling also regulates apicoplast metabolism. Therefore, in this review, we will focus on the role of apicoplast in malaria biology and its metabolic regulation through Ca signaling.

The Multistage Antimalarial Compound Calxinin Perturbates P. falciparum Ca2+ Homeostasis by Targeting a Unique Ion Channel

“…Yet, Ca 2+ signaling and homeostasis are just as critical for the Pf life cycle. This includes key steps in host cell invasion, egress from host cells, and genomic regulation [ 39 , 91 ]. Furthermore, Ca 2+ regulates apicoplast metabolism, which plays a key role in parasite growth [ 92 ].…”

Targeting the Plasmodium falciparum proteome and organelles for potential antimalarial drug candidates

“…The food vacuole of the parasite serves as target sites for antimalarial drugs such as chloroquine, which prevents the bio-crystallisation of haeme ( Teixeira et al, 2011 ). The apicoplast is involved in the synthesis of isoprenoids ( Tewari et al, 2021 ) from isopentenyl pyrophosphate (IPP) in the blood stage of the parasite ( Miller et al, 2014 ; Rai et al, 2017 ). Inhibitors of prokaryotic DNA replication (ciprofloxacin), prokaryotic translation (chloramphenicol, doxycycline ( Okada et al, 2020 ), tetracycline, clindamycin, azithromycin, erythromycin and clarithromycin), a tRNA synthase (mupirocin), and IPP synthesis pathway (fosmidomycin and FR900098) are regarded as targets of apicoplasts ( Uddin et al, 2018 ).…”

The emerging paradigm of calcium homeostasis as a new therapeutic target for protozoan parasites

“…107 Calcium is involved in the exit of merozoites during the asexual life cycle of the malaria parasite and infection of host organisms. 108 Also, calcium plays an essential role in the apicoplast organelle functioning of P. falciparum, which synthesizes isoprenoid molecules and certain lipids important for parasite growth and also uroporphyrinogen responsible for heme to hemozoin conversion in mitochondria. 109 Calcium signaling regulates apicoplast metabolism, playing a key role in P. falciparum growth.…”

“…Calcium signaling is critical for many aspects of the P. falciparum life cycle, host invasion, and genomic regulation 107 . Calcium is involved in the exit of merozoites during the asexual life cycle of the malaria parasite and infection of host organisms 108 . Also, calcium plays an essential role in the apicoplast organelle functioning of P. falciparum , which synthesizes isoprenoid molecules and certain lipids important for parasite growth and also uroporphyrinogen responsible for heme to hemozoin conversion in mitochondria 109 .…”