Extra-glycosomal localisation of Trypanosoma brucei hexokinase 2

Joice, April C.; Lyda, Todd L.; Sayce, Andrew C.; Verplaetse, Emilie; Morris, Meredith T.; Michels, Paul A.M.; Robinson, Derrick R.; Morris, James C.

doi:10.1016/j.ijpara.2012.02.008

Cited by 14 publications

(11 citation statements)

References 43 publications

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“…The TbHK1 is found in glycosomes, while TbHK2 localizes to both glycosomes and the flagellum (Joice et al. ). The enzyme has a high affinity for D‐glucose, yet retains broad substrate specificity.…”

Section: Observations and Predictionsmentioning

confidence: 99%

Comparative Metabolism of Free‐living Bodo saltans and Parasitic Trypanosomatids

Opperdoes

Butenko

Flegontov

et al. 2016

J Eukaryotic Microbiology

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Comparison of the genomes of free-living Bodo saltans and those of parasitic trypanosomatids reveals that the transition from a free-living to a parasitic life style has resulted in the loss of approximately 50% of protein-coding genes. Despite this dramatic reduction in genome size, B. saltans and trypanosomatids still share a significant number of common metabolic traits: glycosomes; a unique set of the pyrimidine biosynthetic pathway genes; an ATP-PFK which is homologous to the bacterial PPi -PFKs rather than to the canonical eukaryotic ATP-PFKs; an alternative oxidase; three phosphoglycerate kinases and two GAPDH isoenzymes; a pyruvate kinase regulated by fructose-2,6-bisphosphate; trypanothione as a substitute for glutathione; synthesis of fatty acids via a unique set of elongase enzymes; and a mitochondrial acetate:succinate coenzyme A transferase. B. saltans has lost the capacity to synthesize ubiquinone. Among genes that are present in B. saltans and lost in all trypanosomatids are those involved in the degradation of mureine, tryptophan and lysine. Novel acquisitions of trypanosomatids are components of pentose sugar metabolism, pteridine reductase and bromodomain-factor proteins. In addition, only the subfamily Leishmaniinae has acquired a gene for catalase and the capacity to convert diaminopimelic acid to lysine.

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Section: Observations and Predictionsmentioning

confidence: 99%

Comparative Metabolism of Free‐living Bodo saltans and Parasitic Trypanosomatids

Opperdoes

Butenko

Flegontov

et al. 2016

J Eukaryotic Microbiology

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show abstract

“…Higher concentrations are required to dissolve intracellular membranes. Using this protocol, cytoplasmic proteins are released at concentrations below 0.05 mg dig/mg PF protein [74]. Lysates were treated with increasing concentrations of digitonin and intact organelles recovered by centrifugation.…”

Section: Glycosomes Biogenesis Is Likely Influenced By Extracellular mentioning

confidence: 99%

Glycosome biogenesis in trypanosomes and the de novo dilemma

Bauer

Morris

2017

PLoS Negl Trop Dis

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Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell. Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis and matrix protein import, have been identified in T. brucei. Based on these findings, it is widely accepted that glycosomes proliferate through growth and division of existing organelles; however, to our knowledge, a de novo mechanism of biogenesis has not been directly demonstrated. Here, we review recent findings that provide support for the existence of an endoplasmic reticulum (ER)-derived de novo pathway of glycosome biogenesis in T. brucei. Two studies recently identified PEX13.1, a peroxin involved in matrix protein import, in the ER of procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been found in the ER of cells undergoing de novo biogenesis of peroxisomes. In addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are important for de novo biogenesis in other eukaryotes. Because glycosomes are rapidly remodeled via autophagy during life cycle differentiation, de novo biogenesis could provide a method of restoring glycosome populations following turnover. Together, the findings we summarize provide support for the hypothesis that glycosome proliferation occurs through growth and division of pre-existing organelles and de novo biogenesis of new organelles from the ER and that the level each mechanism contributes is influenced by glucose availability.

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“…Changes to glycolysis regulation and compartmentalization during kinetoplastid evolution could therefore have provided the necessary selective pressure for loss from the flagellum, or indeed other cellular compartments, of enzymes involved in catabolism of glucose to its glycolytic intermediate 3-phosphoglycerate. In that regard, it is noteworthy that a T. brucei hexokinase isoform (HXK2) dually located in glycosomes and the flagellum [77] is itself catalytically inactive unless co-expressed with the paralogous HXK1, wherein a hexameric recombinant enzyme with kinetic properties similar to native hexokinase purified from T. brucei cells is reconstituted [78]. Tb HXK2 is paralogous to Tb HXK1 , suggesting recent gain of a cytoskeletal function for an abundant trypanosome glycolytic enzyme.…”

Section: Resultsmentioning

confidence: 99%

Evidence for Loss of a Partial Flagellar Glycolytic Pathway during Trypanosomatid Evolution

et al. 2014

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Classically viewed as a cytosolic pathway, glycolysis is increasingly recognized as a metabolic pathway exhibiting surprisingly wide-ranging variations in compartmentalization within eukaryotic cells. Trypanosomatid parasites provide an extreme view of glycolytic enzyme compartmentalization as several glycolytic enzymes are found exclusively in peroxisomes. Here, we characterize Trypanosoma brucei flagellar proteins resembling glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoglycerate kinase (PGK): we show the latter associates with the axoneme and the former is a novel paraflagellar rod component. The paraflagellar rod is an essential extra-axonemal structure in trypanosomes and related protists, providing a platform into which metabolic activities can be built. Yet, bioinformatics interrogation and structural modelling indicate neither the trypanosome PGK-like nor the GAPDH-like protein is catalytically active. Orthologs are present in a free-living ancestor of the trypanosomatids, Bodo saltans: the PGK-like protein from B. saltans also lacks key catalytic residues, but its GAPDH-like protein is predicted to be catalytically competent. We discuss the likelihood that the trypanosome GAPDH-like and PGK-like proteins constitute molecular evidence for evolutionary loss of a flagellar glycolytic pathway, either as a consequence of niche adaptation or the re-localization of glycolytic enzymes to peroxisomes and the extensive changes to glycolytic flux regulation that accompanied this re-localization. Evidence indicating loss of localized ATP provision via glycolytic enzymes therefore provides a novel contribution to an emerging theme of hidden diversity with respect to compartmentalization of the ubiquitous glycolytic pathway in eukaryotes. A possibility that trypanosome GAPDH-like protein additionally represents a degenerate example of a moonlighting protein is also discussed.

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Extra-glycosomal localisation of Trypanosoma brucei hexokinase 2

Cited by 14 publications

References 43 publications

Comparative Metabolism of Free‐living Bodo saltans and Parasitic Trypanosomatids

Comparative Metabolism of Free‐living Bodo saltans and Parasitic Trypanosomatids

Glycosome biogenesis in trypanosomes and the de novo dilemma

Evidence for Loss of a Partial Flagellar Glycolytic Pathway during Trypanosomatid Evolution

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