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Mol Microbiol. 2011 Apr;80(1):117-32. doi: 10.1111/j.1365-2958.2011.07563.x. Epub 2011 Feb 16.

Requirement for acetyl-CoA carboxylase in Trypanosoma brucei is dependent upon the growth environment.

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1
Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.

Abstract

Trypanosoma brucei, the causative agent of human African trypanosomiasis, possesses two fatty acid synthesis pathways: a major de novo synthesis pathway in the ER and a mitochondrial pathway. The 2-carbon donor for both pathways is malonyl-CoA, which is synthesized from acetyl-CoA by Acetyl-CoA carboxylase (ACC). Here, we show that T. brucei ACC shares the same enzyme architecture and moderate ∼ 30% identity with yeast and human ACCs. ACC is cytoplasmic and appears to be distributed throughout the cell in numerous puncta distinct from glycosomes and other organelles. ACC is active in both bloodstream and procyclic forms. Reduction of ACC activity by RNA interference (RNAi) resulted in a stage-specific phenotype. In procyclic forms, ACC RNAi resulted in 50-75% reduction in fatty acid elongation and a 64% reduction in growth in low-lipid media. In bloodstream forms, ACC RNAi resulted in a minor 15% decrease in fatty acid elongation and no growth defect in culture, even in low-lipid media. However, ACC RNAi did attenuate virulence in a mouse model of infection. Thus the requirement for ACC in T. brucei is dependent upon the growth environment in two different life cycle stages.

PMID:
21306439
PMCID:
PMC3656591
DOI:
10.1111/j.1365-2958.2011.07563.x
[Indexed for MEDLINE]
Free PMC Article
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