A Plastid of Probable Green Algal Origin in Apicomplexan Parasites

Köhler, Sabine; Delwiche, Charles F.; Denny, Paul W.; Tilney, Lewis G.; Webster, Paul; Wilson, Robert; Palmer, Jeffrey D.; Roos, David S.

doi:10.1126/science.275.5305.1485

Cited by 708 publications

(487 citation statements)

References 35 publications

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“…An alignment of these sequences was used to create the consensus sequence shown in Figure 2. It is noteworthy that the similarity dendogram that was generated by the Genetics Computer Group (GCG) program ' pileup ' when these sequences were aligned was similar to the phylogenetic relationship of these organisms deduced by a comparison of tufA genes [36].…”

Section: Gene Sequences For D I and H Subunitsmentioning

confidence: 92%

Mechanism and regulation of Mg-chelatase

Walker

Willows

1997

Biochemical Journal

229

173

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Mg-chelatase catalyses the insertion of Mg into protoporphyrin IX (Proto). This seemingly simple reaction also is potentially one of the most interesting and crucial steps in the (bacterio)chlorophyll (Bchl/Chl)-synthesis pathway, owing to its position at the branch-point between haem and Bchl/Chl synthesis. Up until the level of Proto, haem and Bchl/Chl synthesis share a common pathway. However, at the point of metal-ion insertion there are two choices: Mg2+ insertion to make Bchl/Chl (catalysed by Mg-chelatase) or Fe2+ insertion to make haem (catalysed by ferrochelatase). Thus the relative activities of Mg-chelatase and ferrochelatase must be regulated with respect to the organism's requirements for these end products . How is this regulation achieved? For Mg-chelatase, the recent design of an in vitro assay combined with the identification of Bchl-biosynthetic enzyme genes has now made it possible to address this question. In all photosynthetic organisms studied to date, Mg-chelatase is a three-component enzyme, and in several species these proteins have been cloned and expressed in an active form. The reaction takes place in two steps, with an ATP-dependent activation followed by an ATP-dependent chelation step. The activation step may be the key to regulation, although variations in subunit levels during diurnal growth may also play a role in determining the flux through the Bchl/Chl and haem branches of the pathway.

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Section: Gene Sequences For D I and H Subunitsmentioning

confidence: 92%

Mechanism and regulation of Mg-chelatase

Walker

Willows

1997

Biochemical Journal

229

173

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“…Distinctive features of Apicomplexa include a specialized apical invasion machinery, termed the apical complex, and a relict plastid derived from a red algal secondary endosymbiont known as the apicoplast [1,2]. The human parasites Plasmodium spp.…”

Section: Apicomplexan Mitochondria -A Missing Link and An Absent Cyclementioning

confidence: 99%

“…In Plasmodium asexual blood stages there is minimal flux from glycolysis into the TCA, which is instead predominantly driven by glutaminolysis [26,46,47] and has been thought to have a role in maintenance of ubiquinone levels for pyrimidine biosynthesis. Essential to this is production of the reducing equivalents FADH 2 and NAD(P)H, which in most eukaryotes are primarily supplied by the TCA cycle through the activity of succinate dehydrogenase (SDH) for FADH 2 , and IDH, /-ketoglutarate dehydrogenase (KGDH), and malate dehydrogenase (MDH) for NAD(P)H, although the latter is replaced by MQO in Plasmodium (Figure 2). Interestingly, MQO and FH aside, disruption or chemical inhibition of TCA enzymes does not affect asexual development (Figure 1) [26,36,43].…”

Section: Mitochondrial Metabolism Across the Alveolatamentioning

confidence: 99%

Apicomplexan Energy Metabolism: Carbon Source Promiscuity and the Quiescence Hyperbole

Jacot

Waller

Soldati‐Favre

et al. 2016

Trends in Parasitology

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Pages 15apicomplexan mitochondrion in energy generation has remained unclear, given the glucosereplete intracellular nature of the environmental niches of these parasites and the apparent reduction of mitochondrial metabolic pathways [4][5][6][7]. For example, apicomplexan mitochondria lack 'type I' NADH dehydrogenase (NDH, complex I of the ETC) and many apparently lack the enzymes and transporters required for fatty acid b-oxidation [8,9]. Furthermore, the pyruvate dehydrogenase complex (PDH) responsible for conversion of pyruvate into acetyl-CoA -an obligate fuel for the TCA cycle -is only present in the apicoplast [10]. Consequently, there was no obvious entry point to allow catalysis of glycolytic pyruvate by the TCA cycle [10][11][12][13][14]. Despite this, there is overwhelming evidence that apicomplexans rely on a functional and canonical TCA cycle (as reviewed [4,5,15]), and apicomplexan genome annotations indicate the presence of all enzymes of the TCA cycle. Only one clade of apicomplexans, Cryptosporidium spp., show evidence of outright loss of the TCA cycle, but these taxa retain only a highly reduced mitochondrion, the mitosome, and have also lost their apicoplast [5,8,16].This review highlights how metabolomics technologies coupled to genetic manipulation have helped in unraveling apicomplexan parasite plasticity in carbon source utilization through different life stages, revealing a complex and sometimes counter-intuitive pattern of metabolic gains, losses, and reassignments. These changes have presumably been tailored to allow these parasites to thrive within their various host niches, but may constitute some much-needed Achilles' heels in the fight against these devastating diseases. Plasmodium falciparum and the Glycolytic DeceitGlycolysis has long appeared to be the main source of ATP and NAD(P)H in the erythrocytic stages of the malaria parasites, [5,[17][18][19][20][21]. Indeed, glucose uptake in P. falciparum-infected red blood cells (RBCs) has been observed to increase 75-100-fold compared to uninfected RBC [22][23][24][25]. Up to 93% of glucose is converted directly to lactate in asexual stages [26][ 4 _ T D $ D I F F ] and is ultimately excreted into the surrounding host cell. Perturbation of glucose uptake is detrimental to parasite growth [27,28], suggesting that glycolysis is an important part of the parasite's strategy for rapid proliferation. In a manner analogous to the Warburg effect observed in highly-proliferative cancer lines and other rapidly-growing cells (e.g., yeast and bloodstream Trypanosoma spp.), Plasmodium (in erythrocytic stages) has opted for fast generation of ATP through substrate-level phosphorylation and secretion of lactate as an end-product (aerobic fermentative glycolysis), as opposed to the 'slow but efficient' mitochondrial oxidative phosphorylation and complete oxidation [29]. Reasons for this dependence on glycolytic fermentation remain unclear -after all, blood stages of Plasmodium certainly have access to oxygen -but it may be a way of avoiding excessiv...

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“…Based on data showing that it contains a 35 kb DNA molecule similar to that found in the chloroplast genome, the term apicoplast has been suggested for this organelle (Kohler et al 1997). The presence of the four unit membranes surrounding the apicoplast has been interpreted as evidence that it originated as a secondary endosymbiont derived by ingestion of a eukaryote that itself harbored a plastid, analogous to the plastids of chlorarachniophytes and cryptomonads.…”

Section: Cell Fractionation Of Apicomplexamentioning

confidence: 99%

Cell fractionation of parasitic protozoa: a review

Souza

Cunha-e-Silva

2003

Mem. Inst. Oswaldo Cruz

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Cell fractionation, a methodological strategy for obtaining purified organelle preparations, has been applied successfully to parasitic protozoa by a number of investigators. Here we present and discuss the work of several groups that have obtained highly purified subcellular fractions from trypanosomatids, Apicomplexa and trichomonads, and whose work have added substantially to our knowledge of the cell biology of these parasites.

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A Plastid of Probable Green Algal Origin in Apicomplexan Parasites

Cited by 708 publications

References 35 publications

Mechanism and regulation of Mg-chelatase

Mechanism and regulation of Mg-chelatase

Apicomplexan Energy Metabolism: Carbon Source Promiscuity and the Quiescence Hyperbole

Cell fractionation of parasitic protozoa: a review

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