What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2011 Jan 18
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

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1.	Eukaryot Cell. 2011 Jan 14. [Epub ahead of print] Depletion of mitochondrial acyl carrier protein in bloodstream form Trypanosoma brucei causes a kinetoplast segregation defect. Clayton AM, Guler JL, Povelones ML, Gluenz E, Gull K, Smith TK, Jensen RE, Englund PT. Departments of Biological Chemistry and Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD USA; Sir William Dunn School of Pathology, University of Oxford, Oxford UK; Centre for Biomolecular Sciences, The University, St. Andrews, Scotland UK. Abstract Like other eukaryotes, trypanosomes have an essential type II fatty acid synthase in their mitochondrion. We have investigated the function of this synthase in bloodstream form parasites by studying the effect of a conditional knockout of acyl carrier protein (ACP), a key player in this fatty acid synthase pathway. We found that ACP depletion caused not only small changes in cellular phospholipids, but it also, surprisingly, caused changes in the kinetoplast. This structure, which contains the mitochondrial genome in the form of a giant network of several thousand interlocked DNA rings (kinetoplast DNA or kDNA), became larger in some cells and smaller or absent in others. We observed the same pattern in isolated networks, viewed either by fluorescence or electron microscopy. We found that the changes in kDNA size are not due to the disruption of replication, but instead, a defect in segregation. kDNA segregation is mediated by the tripartite attachment complex (TAC) and we hypothesize that one of the TAC components, a differentiated region of the mitochondrial double membrane, has an altered phospholipid composition when ACP is depleted. We further speculate that this compositional change affects TAC function and thus, kDNA segregation.
	PMID: 21239625 [PubMed - as supplied by publisher]
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2.	J Biol Chem. 2011 Jan 14. [Epub ahead of print] Dissecting the metabolic roles of pteridine reductase 1 in Trypanosoma brucei and Leishmania major. Ong HB, Sienkiewicz N, Wyllie S, Fairlamb AH. University of Dundee, United Kingdom. Abstract Leishmania parasites are pteridine auxotrophs that use an NADPH-dependent pteridine reductase 1 (PTR1) and NADH-dependent quinonoid dihydropteridine reductase (QDPR) to salvage and maintain intracellular pools of tetrahydrobiopterin (H(4)B). However, the African trypanosome lacks a credible candidate QDPR in its genome despite maintaining apparent QDPR activity. Here we provide evidence that the NADH-dependent activity previously reported by others is an assay artefact. Using an HPLC-based enzyme assay, we demonstrate that there is an NADPH-dependent QDPR activity associated with both TbPTR1 and LmPTR1. The kinetic properties of recombinant PTR1s are reported at physiological pH and ionic strength and compared with LmQDPR. Specificity constants (k(cat)/K(m)) for LmPTR1 are similar with dihydrobiopterin (H(2)B) and quinonoid dihydrobiopterin (q H(2)B) as substrates and about 20-fold lower than LmQDPR with q H(2)B. In contrast, TbPTR1 shows a 10-fold higher k(cat)/K(m) for H(2)B over q H(2)B. Analysis of T. brucei isolated from infected rats revealed that tetrahydrobiopterin (H(4)B; 430 nM, 98% of total biopterin) was the predominant intracellular pterin, consistent with a dual role in the salvage and regeneration of H(4)B. Gene knockout experiments confirmed this: PTR1 nulls could only be obtained from lines overexpressing LmQDPR with H(4)B as a medium supplement. These cells grew normally with H(4)B, which spontaneously oxidises to q H(2)B, but were unable to survive in the absence of pterin or with either biopterin or H(2)B in the medium. These findings establish that PTR1 has an essential and dual role in pterin metabolism in African trypanosomes and underline its potential as a drug target.
	PMID: 21239486 [PubMed - as supplied by publisher]
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