Biology:Apicoplast
An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including Toxoplasma gondii, and Plasmodium falciparum and other Plasmodium spp. (parasites causing malaria), but not in others such as Cryptosporidium. It originated from algae through secondary endosymbiosis; there is debate as to whether this was a green or red alga. The apicoplast is surrounded by four membranes within the outermost part of the endomembrane system.[1] The apicoplast hosts important metabolic pathways like fatty acid synthesis, 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 phylum Apicomplexa.[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 and 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 Apicomplexa 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's nucleus and often closely associated with a mitochondrion. 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 some RNAs.[8] Particles suspected to be bacterial ribosomes are present.[5] The plastid, at least in the Plasmodium species, also contains "tubular whorls" of membrane that bear a striking resemblance to the 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 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.[5]
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 MEP pathway for isoprenoid precursor synthesis and is the sole site for such synthesis in the Plasmodium cell.[1]
Heme synthesis
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]
References
- ↑ 1.0 1.1 1.2 1.3 "The evolution, metabolism and functions of the apicoplast". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 365 (1541): 749–63. March 2010. doi:10.1098/rstb.2009.0273. PMID 20124342.
- ↑ "The metabolic roles of the endosymbiotic organelles of Toxoplasma and Plasmodium spp". Current Opinion in Microbiology 16 (4): 452–8. August 2013. doi:10.1016/j.mib.2013.07.003. PMID 23927894.
- ↑ Reece, Jane B.; Urry, Lisa A.; Cain, Michael L.; Wasserman, Steven A.; Minorsky, Peter V.; Jackson, Robert B. (2011). Campbell Biology (9th ed.). Boston: Benjamin Cummings. ISBN 978-0-321-55823-7. OCLC 1008837408. https://archive.org/details/campbellbiologyj00reec.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 "The apicoplast: a new member of the plastid family". Trends in Plant Science 6 (5): 200–5. May 2001. doi:10.1016/s1360-1385(01)01921-5. PMID 11335172.
- ↑ 5.0 5.1 5.2 5.3 5.4 "The apicoplast as an antimalarial drug target". Drug Resistance Updates 4 (3): 145–51. June 2001. doi:10.1054/drup.2001.0205. PMID 11768328.
- ↑ "Evolutionary pressures on apicoplast transit peptides". Molecular Biology and Evolution 21 (12): 2183–94. December 2004. doi:10.1093/molbev/msh233. PMID 15317876.
- ↑ Alberts, Bruce; Bray, Dennis; Hopkin, Karen (2004). "The Eukaryotic Cell". Essential Cell Biology (2nd ed.). New York; London: Garland Science, Taylor & Francis Group. ISBN 978-0-8153-3480-4. OCLC 895254951. https://archive.org/details/essentialcellbio00albe.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Kimball, John W. (16 December 2017). "Endosymbiosis and The Origin of Eukaryotes". Kimball's Biology Pages. http://www.biology-pages.info:80/E/Endosymbiosis.html.
- ↑ "Protein sorting in complex plastids". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1833 (2): 352–9. February 2013. doi:10.1016/j.bbamcr.2012.05.030. PMID 22683761.
- ↑ "Toxoplasma gondii Toc75 Functions in Import of Stromal but not Peripheral Apicoplast Proteins". Traffic 16 (12): 1254–69. December 2015. doi:10.1111/tra.12333. PMID 26381927. http://eprints.gla.ac.uk/114861/7/114861.pdf.
- ↑ "Genetic evidence that an endosymbiont-derived endoplasmic reticulum-associated protein degradation (ERAD) system functions in import of apicoplast proteins". The Journal of Biological Chemistry 284 (48): 33683–91. November 2009. doi:10.1074/jbc.M109.044024. PMID 19808683.
- ↑ "Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum". Antimicrobial Agents and Chemotherapy 50 (9): 3124–31. September 2006. doi:10.1128/AAC.00394-06. PMID 16940111.
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