Journal
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
Volume 170, Issue 1, Pages 41-44Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molbiopara.2009.11.002
Keywords
Leishmania; Glycosome; Hexokinase; Glucose toxicity; PTS2
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Funding
- CDRI, Lucknow, India [SIP0026]
- Council of Scientific and Industrial Research, New Delhi
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Compartmentalization of glycolytic enzymes in glycosomes is vital in trypanosomatid parasites. Retention of these enzymes in the cytosol induces sugar toxicity and accumulation of intermediate metabolites, notably the hexokinase product glucose-6-phosphate. However, the role of hexokinase in sugar mediated toxicity remains unexplored. We have generated Leishmania donovani transfectants expressing a catalytically active cytosolic mutant of hexokinase. In the presence of glucose. these transfectants exhibited toxicity during log and stationary phases of growth. These results suggest that targeting of hexokinase to the glycosome is required to prevent uncontrolled and cytotoxic glucose phosphorylation in L. donovani parasites. (C) 2009 Elsevier B.V. All rights reserved.
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