Anapicoplast is aderived non-photosyntheticplastid found in mostApicomplexa, includingToxoplasma gondii, andPlasmodium falciparum and otherPlasmodium spp. (parasites causingmalaria), but not in others such asCryptosporidium. It originated fromalgae throughsecondary endosymbiosis; there is debate as to whether this was agreen orred alga. The apicoplast is surrounded by four membranes within the outermost part of the endomembrane system.[1] The apicoplast hosts important metabolic pathways likefatty acid synthesis,isoprenoid precursor synthesis and parts of theheme biosynthetic pathway.[2]
Apicoplasts are arelict, nonphotosyntheticplastid found in mostprotozoan parasites belonging to thephylumApicomplexa.[3][4] Among the most infamous apicomplexan parasites isPlasmodium falciparum, a causative agent of severemalaria. Because apicoplasts are vital to parasite survival, they provide an enticing target for antimalarial drugs.[5] Specifically, apicoplasts' plant-like properties provide a target forherbicidal 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]
Evidence suggests that the apicoplast is a product of secondaryendosymbiosis,[6] and that the apicoplast may be homologous to the secondary plastid of the closely relateddinoflagellate 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 anucleomorph.[8]
MostApicomplexa contain a single ovoid shaped apicoplast that is found at the anterior of the invading parasitic cell.[4] The apicoplast is situated in close proximity to the cell'snucleus and often closely associated with amitochondrion. The small plastid, only 0.15–1.5 μm in diameter,[4] is surrounded by four membranes.[8] The two inner membranes are derived from the algal plastid membranes;[4] the next membrane out is called the periplastid membrane and is derived from the algal plasma membrane; Finally the outermost membrane belongs to the host endomembrane system.[9] Within the apicoplast's stroma is a 35 kb long circular DNA strand that codes for approximately 30 proteins,tRNAs and someRNAs.[8] Particles suspected to be bacterialribosomes are present.[5] The plastid, at least in thePlasmodium species, also contains "tubular whorls" of membrane that bear a striking resemblance to thethylakoids[4] of theirchloroplast 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 theendoplasmic-reticulum-associated protein degradation (for example:[11]).
The apicoplast is a vitalorganelle to the parasite's survival.[4]Tetracycline, an antibiotic also used to combatmalaria infections, is thought to function by targeting the apicoplast.[12] It hosts four main metabolic pathways:
The destruction of the apicoplast does not immediately kill theparasite but instead prevents it from invading new host cells. This observation suggests that the apicoplast may be involved inlipidmetabolism. If unable to synthesize sufficientfatty acids, the parasite is unable to form the parasitophorousvacuole (PV) that is imperative to a successful invasion of host cells. This conclusion is supported by the discovery oftype II fatty acid synthase (FAS) machinery in the apicoplast.[5]
The apicoplast is also thought to have a role inisoprenoid synthesis, which are prosthetic groups on many enzymes and also act as precursors toubiquinones (involved in electron transport) anddolichols (involved inglycoprotein formation).[1] The apicoplast contains the2-C-Methyl-D-erythritol 4-phosphate (MEP)/1-deoxy-D-xylulose-5-phosphate (DOXP) pathway for isoprenoid precursor synthesis and is the sole site for such synthesis in thePlasmodium cell.[1]
The apicoplast has also been implicated withheme synthesis[5] andamino 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]
Various iron-sulphur cluster biosynthetic enzymes including SufB or Orf470 have been identified in the apicoplast genome.[1]