Hundreds of millions of people all over the world suffer from malaria; hence, the millennium struggle to get it under control has pushed researchers to explore a multitude of scientific avenues to try and find any exploitable flaws in the malaria parasite, Plasmodium falciparum. One of the discoveries made is the apicoplast, which is a chloroplast found within this and other apicomplexan parasites. This organelle, a remnant of the photosynthetic ancestor of the parasite, has recently attracted great interest because of its unusual biological pathways and as a potential drug target. Together with its unique origin and metabolic functions, the fact that the apicoplast plays a crucial role in the life cycle of the parasite offers promising avenues for the development of new antimalarial therapies. The article below sheds some light on the multifaceted roles of the apicoplast, why it is an important factor, and its potential in the ongoing battle to squash malaria.
History and Structure of Apicoplast
The apicoplast seems to be an organelle essentially required in Plasmodium falciparum, and its evolutionary history is intriguing. Probably one of the most complex events to have occurred would be that of a secondary endosymbiosis event involving an ancestral eukaryote engulfing a red alga itself, already containing a primary chloroplast from a cyanobacterium. This organelle has lost its photosynthetic capability over time but has retained other vital functions necessary for survival.
The apicoplast is bound by four membranes, an ultra-structural feature that reflects its colorful evolutionary history. The outer two of these membranes are derived from the host membranes of the endomembrane system, while the inner two represent various algal and cyanobacteria membranes. This structure has implications for its function and for the targeting of proteins synthesized in the cytosol and transported into the apicoplast.
Functions of the Apicoplast
The apicoplast performs various critical activities within the malaria parasite’s biology. Therefore, key activities are metabolic pathways absent in the human host, making it an attractive target for antimalarial drugs. One of the most critical functions of apicoplasts is fatty acid synthesis. The apicoplast contains enzymes involved in the type II fatty acid synthesis pathway. The latter is different from the type I fatty acid synthase found in humans. This pathway is required for the synthesis of fatty acids involved in membrane biogenesis and parasite replication. Thus, inhibition of the enzymes in the FASII pathway will disrupt the life cycle of the parasite; therefore, such enzymes could become prime targets for drug development against this infection.
Another critical pathway in the apicoplast is the non-mevalonate pathway of isoprenoid biosynthesis. This pathway produces the isoprenoids, which are dysfunctional molecules involved in electron transport, cell membrane maintenance, and protein prenylation. The fact that this pathway does not exist in humans brings the apicoplast forward as a selective drug target.
Heme and Iron-Sulfur Cluster Biosynthesis: The apicoplast also participates in the biosynthesis of heme and iron-sulfur clusters, two important cofactors in hundreds of different enzymatic reactions. Apicoplast synthesis of heme complements the heme derived from the host erythrocytes to provide adequate amounts to meet the metabolic demands of the parasite. Iron-sulfur clusters play a crucial role in electron transfer reactions and other metabolic processes.