isoprenoid precursor synthesis and parts of the heme biosynthetic pathway.[2]
Significance
Apicoplasts are a relict, nonphotosynthetic plastid found in most protozoan parasites belonging to the phylumApicomplexa.[3][4] Among the most infamous apicomplexan parasites is Plasmodium falciparum, a causative agent of severe malaria. Because apicoplasts are vital to parasite survival, they provide an enticing target for antimalarial drugs.[5] Specifically, apicoplasts' plant-like properties provide a target for herbicidal drugs.[4] And, with the emergence of malarial strains resistant to current treatments it is paramount that novel therapies, like herbicides, are explored and understood.[5] Furthermore, herbicides may be able to specifically target the parasite's plant-like apicoplast without any noticeable effect on the mammalian host's cells.[citation needed]
Evolutionary origin
Evidence suggests that the apicoplast is a product of secondary
endosymbiosis,[6] and that the apicoplast may be homologous to the secondary plastid of the closely related dinoflagellate algae. An ancient cyanobacterium was first engulfed by a eukaryotic cell but was not digested. The bacterium escaped being digested because it formed a symbiotic relationship with the host eukaryotic cell; both the eukaryote and the bacterium mutually benefited from their novel shared existence.[7] The result of the primary endosymbiosis was a photosynthetic eukaryotic alga. A descendant of this eukaryotic alga was then itself engulfed by a heterotrophic eukaryote with which it formed its own symbiotic relationship and was preserved as a plastid.[8] The apicoplast evolved in its new role to preserve only those functions and genes necessary to beneficially contribute to the host-organelle relationship. The ancestral genome of more than 150 kb was reduced through deletions and rearrangements to its present 35 kb size.[4] During the reorganization of the plastid the apicoplast lost its ability to photosynthesize.[8] These losses of function are hypothesized to have occurred at an early evolutionary stage in order to have allowed sufficient time for the complete degradation of acknowledged photosynthetic relicts[4] and the disappearance of a nucleomorph.[8]
Architecture and distribution
Most
thylakoids[4] of their chloroplast relatives.[8] The import of proteins into the apicoplast through the four membranes occurs through translocation complexes that originate from the algal plastid (for example: [10]) or from a duplication of the endoplasmic-reticulum-associated protein degradation (for example: [11]
).
Function
The apicoplast is a vital organelle to the parasite's survival.[4]Tetracycline, an antibiotic also used to combat malaria infections, is thought to function by targeting the apicoplast.[12] It hosts four main metabolic pathways:
Fatty acid synthesis
The destruction of the apicoplast does not immediately kill the
parasite but instead prevents it from invading new host cells. This observation suggests that the apicoplast may be involved in lipidmetabolism. If unable to synthesize sufficient fatty acids the parasite is unable to form the parasitophorous vacuole (PV) that is imperative to a successful invasion of host cells. This conclusion is supported by the discovery of type II fatty acid synthase (FAS) machinery in the apicoplast.[5]
The apicoplast has also been implicated with heme synthesis[5] and amino acid synthesis. It is also suggested to have a role in cell development. These functions, however, are merely postulations and are not yet conclusively supported by experimentation.[4]
Iron-sulphur cluster synthesis
Various iron-sulphur cluster biosynthetic enzymes including SufB or Orf470 have been identified in the apicoplast genome.[1]
