title: Glucose is toxic to glycosome-deficient trypanosomes.
abstract: Trypanosomatids, the etiologic agents of sleeping sickness, leishmaniasis, and Chagas' disease, compartmentalize glycolysis within glycosomes, metabolic organelles related to peroxisomes. Here, we identify a trypanosome homologue of PEX14, one of the components of the peroxisomal protein import docking complex. We have used double-stranded RNA interference to target the PEX14 transcript for degradation. Glycosomal matrix protein import was compromised, and both glycolytic bloodstream stage parasites and mitochondrially respiring procyclic stage parasites were killed. Thus, unlike peroxisomes, glycosomes are essential organelles. Surprisingly, procyclic forms, which can grow in the absence of glucose, were killed by PEX14 RNA interference only when simple sugars were present. Thus, interference with glycosome protein import makes glucose toxic to trypanosomes.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Furuya
authors.forename: Peter
authors.initials: P
authors.lastname: Kessler
authors.forename: Armando
authors.initials: A
authors.lastname: Jardim
authors.forename: Achim
authors.initials: A
authors.lastname: Schnaufer
authors.forename: Christopher
authors.initials: C
authors.lastname: Crudder
authors.forename: Marilyn
authors.initials: M
authors.lastname: Parsons
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003470:Culture Media; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008830:Microbodies / Q000378:metabolism; D008969:Molecular Sequence Data; D020675:Peroxisomes / Q000378:metabolism; D010735:Phosphoglycerate Kinase / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D003470:Culture Media; D008565:Membrane Proteins; C468927:PEX14 protein, Trypanosoma brucei; D015800:Protozoan Proteins; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D010735:Phosphoglycerate Kinase; D005947:Glucose