Apicoplast

An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including malaria parasites such as Plasmodium falciparum, but not in others such as Cryptosporidium. It originated from an alga (there is debate as to whether this was a green or red alga) through secondary endosymbiosis. The apicoplast is surrounded by four membranes within the outermost part of the endomembrane system.[1]

Significance

Apicoplasts are a relict, nonphotosynthetic plastid found in most protozoan parasites belonging to the phylum Chromalveolata.[2][3] Among the most infamous Chromalveolata 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.[4] Specifically, apicoplasts' plant-like properties provide a target for herbicidal drugs.[3] And, with the emergence of malarial strains resistant to current treatments it is paramount that novel therapies, like herbicides, are explored and understood.[4] Furthermore, herbicides may be able to specifically target the parasite's plant-like apicoplast and without any noticeable effect on the mammalian host's cells.

Evolutionary origin

Evidence suggests that the apicoplast is a product of secondary endosymbiosis,[5] 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.[6] The result of the primary endosymbiosis was a photosynthetic eukaryotic alga. A descendent 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.[7] The apicoplast plastid 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.[3] During the reorganization of the plastid the apicoplast lost its ability to photosynthesize.[7] 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[3] and the disappearance of a nucleomorph.[7]

Architecture and distribution

Most Apicomplexa contain a single ovoid shaped apicoplast that is found at the anterior of the invading parasitic cell.[3] The apicoplast is situated in close proximity to the cell's nucleus and always closely associated with a mitochondrion. The small plastid, only 0.15-1.5 μm in diameter,[3] is surrounded by four membranes.[7] The two inner membranes are called the outer (OEM) and inner envelope membrane (IEM) and are derived from the plastid envelope.[3] Within the apicoplast's membrane is a 35 kb long circular DNA strand that codes for approximately 30 proteins, tRNAs and some RNAs.[7] Particles suspected to be bacterial ribosomes are present.[4] The plastid, at least in the Plasmodium species, also contains "tubular whorls" of membrane that bear a striking resemblance to the thylakoids[3] of their chloroplast relatives.[7]

Function

The functions of apicoplasts have not been conclusively defined. However, it has been established that the apicoplast is a vital organelle to the parasite's survival.[3] Tetracycline, an antibiotic also used to combat malaria infections, is thought to function by targeting the apicoplast.[8]

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 lipid metabolism. 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.[4]

Isoprenoid Synthesis

The apicoplast is also thought to have a role in isoprenoid synthesis, which are prosthetic groups on many enzymes and also act as precursors to ubiquinones (involved in electron transport) and dolichols (involved in glycoprotein formation).[1] The apicoplast contains the DOXP pathway for isoprenoid synthesis and is the sole site for synthesis in the Plasmodium genome.[1]

Heme synthesis

The apicoplast has also been implicated with heme synthesis[4] 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.[3]

Iron-sulphur cluster synthesis

Various iron-sulphur cluster biosynthetic enzymes including SufB or Orf470 have been identified in the apicoplast genome.[1]

References

  1. 1 2 3 4 Lim, L.; McFadden, G. (2010). "The evolution, metabolism and functions of the apicoplast". Philosophical Transactions of the Royal Society. 365: 749–763. doi:10.1098/rstb.2009.0273. PMC 2817234Freely accessible. PMID 20124342.
  2. ↑ Biology 9th edition by Reece, Urry, Cain, Wasserman, Minorsky, Jackson
  3. 1 2 3 4 5 6 7 8 9 10 Maréchal, E.; et al. (2001). "The Apicoplast: a new member of the plastid family" (PDF). Biology of the Cell. 6 (5): 200–205. doi:10.1016/s1360-1385(01)01921-5.
  4. 1 2 3 4 5 Ralph, S.; et al. (2001). "The apicoplast as an antimalarial drug target" (– Scholar search). Drug Resistance Updates. 4 (3): 145–151. doi:10.1054/drup.2001.0205. PMID 11768328.
  5. ↑ Ralph, S.; et al. (2004). "Evolutionary Pressures on Apicoplast Transit Peptides" (– Scholar search). Molecular Biology and Evolution. 21 (12): 2183–2191. doi:10.1093/molbev/msh233. PMID 15317876.
  6. ↑ Essential Cell Biology, 2nd ed. "The Eukaryotic Cell.".
  7. 1 2 3 4 5 6 "Endosymbiosis and The Origin of Eukaryotes". 2006-05-24.
  8. ↑ Dahl, E. L.; Shock, J. L.; Shenai, B. R.; Gut, J.; DeRisi, J. L.; Rosenthal, P. J. (2006). "Tetracyclines Specifically Target the Apicoplast of the Malaria Parasite Plasmodium falciparum". Antimicrobial Agents and Chemotherapy. 50 (9): 3124–3131. doi:10.1128/AAC.00394-06. ISSN 0066-4804.
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