Document Detail


Requirement for acetyl-CoA carboxylase in Trypanosoma brucei is dependent upon the growth environment.
MedLine Citation:
PMID:  21306439     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Patrick A Vigueira; Kimberly S Paul
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-16
Journal Detail:
Title:  Molecular microbiology     Volume:  80     ISSN:  1365-2958     ISO Abbreviation:  Mol. Microbiol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-25     Completed Date:  2011-07-15     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8712028     Medline TA:  Mol Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-32     Citation Subset:  IM    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
Affiliation:
Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetyl-CoA Carboxylase / genetics,  metabolism*
Animals
Blotting, Northern
Female
Mice
RNA Interference
Signal Transduction / genetics,  physiology
Trypanosoma brucei brucei / enzymology*,  genetics,  growth & development*
Grant Support
ID/Acronym/Agency:
1R15AI081207/AI/NIAID NIH HHS; R15 AI081207/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
EC 6.4.1.2/Acetyl-CoA Carboxylase
Comments/Corrections

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