Molecular identification and characterization of an essential pyruvate transporter from trypanosoma brucei

Marco Sanchez

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Pyruvate export is an essential physiological process for the bloodstream form of Trypanosoma brucei as the parasite would otherwise accumulate this end product of glucose metabolism to toxic levels. In the studies reported here, genetic complementation in Saccharomyces cerevisiae has been employed to identify a gene (TbPT0) that encodes this vital pyruvate transporter from T. brucei. Expression of TbPT0 in S. cerevisiae reveals that TbPT0 is a high affinity pyruvate transporter. TbPT0 belongs to a clustered multigene family consisting of five members, whose expression is up-regulated in the bloodstream form. Interestingly, TbPT family permeases are related to polytopic proteins from plants but not to characterized monocarboxylate transporters from mammals. Remarkably, inhibition of the TbPT gene family expression in bloodstream parasites by RNAi is lethal, confirming the physiological relevance of these transporters. The discovery of TbPT0 reveals for the first time the identity of the essential pyruvate transporter and provides a potential drug target against the mammalian life cycle stage of T. brucei.

Original languageEnglish (US)
Pages (from-to)14428-14437
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number20
DOIs
StatePublished - May 17 2013

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Trypanosoma brucei brucei
Yeast
Saccharomyces cerevisiae
Parasites
Genes
Physiological Phenomena
Plant Proteins
Mammals
Membrane Transport Proteins
Poisons
Multigene Family
RNA Interference
Life Cycle Stages
Pyruvic Acid
Metabolism
Life cycle
Gene Expression
Glucose
Pharmaceutical Preparations
pyruvate transport protein

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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Molecular identification and characterization of an essential pyruvate transporter from trypanosoma brucei. / Sanchez, Marco.

In: Journal of Biological Chemistry, Vol. 288, No. 20, 17.05.2013, p. 14428-14437.

Research output: Contribution to journalArticle

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