Glucose is toxic to glycosome-deficient trypanosomes.
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.
Furuya
Tetsuya
T
Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Kessler
Peter
P
Jardim
Armando
A
Schnaufer
Achim
A
Crudder
Christopher
C
Parsons
Marilyn
M
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
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