Chapter 14 : The Apicoplast

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The discovery and characterization of the apicoplast has been one of the success stories for the growing union of molecular, cellular, and genomic biology in parasitology. The combination of these three disciplines in a short space of time has shed much light on the origin, structure, biogenesis, and metabolism of the apicoplast. The apicoplast contains visible ribosomes, distinctly smaller than the eukaryotic cytosolic ribosomes, and is surrounded by multiple membranes. The dissection of apicoplast targeting by Waller using green fluorescent protein (GFP), alongside similar constructs made in the laboratory of David Roos, inspired an ongoing series of broader targeting experiments in both and that have revolutionized the understanding of intra- and extracellular trafficking in apicomplexans. The fluoroquinolone compound ciprofloxacin interferes with the resealing step and results in linearization of the circular DNA, and ciprofloxacin does indeed inhibit displacement-loop replication in . Antibiotics such as ciprofloxacin inhibit bacterial or plastid DNA replication, while other antibiotics affect transcription, translation, and posttranslational modification. An elegant analysis showed that the fusion protein is apparently trapped in the apicoplast protein-translocation machinery and somehow prevents correct division and segregation of the apicoplast. Chloroplasts are chlorophyll-containing organelles found in plants and algae. Their key function is photosynthesis, and they come in red, brown, and even colorless, nonphotosynthetic versions. Products of the isopentenyl diphosphate (IPP) pathway are presumably also used by mitochondrial ubiquinones, by dolichol in the endoplasmic reticulum (ER) and Golgi, and to prenylate proteins within the parasite’s endomembrane system.

Citation: Ralph S. 2005. The Apicoplast, p 272-289. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch14

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Type II Fatty Acid Synthase
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Apicoplasts arise through secondary endosymbiosis. In the primary endosymbiosis that created plastids, a cyanobacterium is engulfed by a heterotrophic eukaryote and retained in the eukaryotic cytosol. The transfer of genes from bacterium to host nucleus reinforces the dependence of the plastid on its new host. Most of the gene products that derive from these transferred genes are targeted back to the plastid with an N-terminal transit peptide. In secondary endosymbiosis, a plastid-bearing organism is itself engulfed and enslaved by an another eukaryote. As with primary endosymbionts, secondary endosymbiosis is characterized by large-scale gene transfer from endosymbiont to host. In most extant secondary endosymbionts, the nucleus of the engulfed eukaryote has completely disappeared through gene transfer and loss. The products of transferred genes are retargeted to the plastid with a bipartite leader consisting of signal sequence and transit peptide. The prey item that eventually became the apicoplast is unknown but is probably a red alga.

Citation: Ralph S. 2005. The Apicoplast, p 272-289. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch14
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The apicoplast delayed-death phenomenon. Some of the inhibitors that are thought to target the apicoplast have delayed effects on parasite growth. Compounds such as ciprofloxacin do not appear to inhibit growth within the initial parasitophorous vacuole, but after the parasite reinvades, parasites cease to divide even when drug is removed. These reinvading parasites are not microscopically distinguishable from untreated parasites but are evidently phenotypically different. This inhibition kinetic is shared at least between (A) and (B). In , parasites with defects in apicoplast segregation mimic the drug-induced delayed death phenotype, with apicoplast-lacking parasites apparently growing normally until after reinvasion (C). One explanation for delayed death, consistent with known apicoplast metabolic functions, is that apicoplasts create a molecule that is needed for appropriate establishment or development of the parasitophorous vacuole membrane. In the absence of this molecule, a nonfunctional or simply nonexpanding parasitophorous vacuole restricts further growth.

Citation: Ralph S. 2005. The Apicoplast, p 272-289. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch14
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Major apicoplast anabolic pathways. Bioinformatic analyses and confirmation by biochemical methods suggest that the apicoplast is responsible for at least four major anabolic pathways, fatty acid synthesis, isopentenyl diphosphate synthesis, iron-sulfur cluster assembly, and heme synthesis, in conjunction with the mitochondrion. Plastid-specific transporters probably import triose phosphates and/or phosphoenolpyruvate to be used as the carbon building blocks for synthesis, as well as generating some energy for synthetic pathways. Each pathway may have organellar uses, but the indispensability of the apicoplast indicates there are also extraplastidic endpoints for at least one of these anabolic pathways.

Citation: Ralph S. 2005. The Apicoplast, p 272-289. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch14
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