Glucose-induced remodeling of intermediary and energy metabolism in procyclic Trypanosoma brucei

Coustou, V., Biran, M., Breton, M., Guegan, F., Riviere, L., Plazolles, N., Nolan, D., Barrett, M.P. , Franconi, J.M. and Bringaud, F. (2008) Glucose-induced remodeling of intermediary and energy metabolism in procyclic Trypanosoma brucei. Journal of Biological Chemistry, 283(24), pp. 16342-16354. (doi:10.1074/jbc.M709592200)

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Publisher's URL: http://dx.doi.org/10.1074/jbc.M709592200

Abstract

The procyclic form of Trypanosoma brucei is a parasitic protozoan that normally dwells in the midgut of its insect vector. In vitro, this parasite prefers D-glucose to L-proline as a carbon source, although this amino acid is the main carbon source available in its natural habitat. Here, we investigated how L-proline is metabolized in glucose-rich and glucose-depleted conditions. Analysis of the excreted end products of C-13-enriched L-proline metabolism showed that the amino acid is converted into succinate or L-alanine depending on the presence or absence of D-glucose, respectively. The fact that the pathway of L-proline metabolism was truncated in glucose-rich conditions was confirmed by the analysis of 13 separate RNA interference-harboring or knock-out cell lines affecting different steps of this pathway. For instance, RNA interference studies revealed the loss of succinate dehydrogenase activity to be conditionally lethal only in the absence of D-glucose, confirming that in glucose-depleted conditions, L-proline needs to be converted beyond succinate. In addition, depletion of the F-0/F-1-ATP synthase activity by RNA interference led to cell death in glucose-depleted medium, but not in glucose-rich medium. This implies that, in the presence of D-glucose, the importance of the F-0/F-1-ATP synthase is diminished and ATP is produced by substrate level phosphorylation. We conclude that trypanosomes develop an elaborate adaptation of their energy production pathways in response to carbon source availability

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Barrett, Professor Michael
Authors: Coustou, V., Biran, M., Breton, M., Guegan, F., Riviere, L., Plazolles, N., Nolan, D., Barrett, M.P., Franconi, J.M., and Bringaud, F.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Biological Chemistry
Journal Abbr.:J Biol Chem.
Publisher:American Society for Biochemistry and Molecular Biology, Inc.
ISSN:0021-9258
ISSN (Online):1083-351X

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