Regulation of Trypanosoma brucei Acetyl Coenzyme A Carboxylase by Environmental Lipids

MSphere
Sunayan S RayKimberly S Paul

Abstract

To satisfy its fatty acid needs, the extracellular eukaryotic parasite Trypanosoma brucei relies on two mechanisms: uptake of fatty acids from the host and de novo synthesis. We hypothesized that T. brucei modulates fatty acid synthesis in response to environmental lipid availability. The first committed step in fatty acid synthesis is catalyzed by acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) and serves as a key regulatory point in other organisms. To test our hypothesis, T. brucei mammalian bloodstream and insect procyclic forms were grown in low-, normal-, or high-lipid media and the effect on T. brucei ACC (TbACC) mRNA, protein, and enzymatic activity was examined. In bloodstream form T. brucei, media lipids had no effect on TbACC expression or activity. In procyclic form T. brucei, we detected no change in TbACC mRNA levels but observed 2.7-fold-lower TbACC protein levels and 37% lower TbACC activity in high-lipid media than in low-lipid media. Supplementation of low-lipid media with the fatty acid stearate mimicked the effect of high lipid levels on TbACC activity. In procyclic forms, TbACC phosphorylation also increased 3.9-fold in high-lipid media compared to low-lipid media. Phosphatase treatment of TbACC increased ...Continue Reading

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Citations

Oct 30, 2020·ELife·Anya J O'NealJoao Hf Pedra

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Methods Mentioned

BETA
acylation
PCR
electrophoresis
gel filtration
immunoprecipitation
pulldown
ubiquitination
protein assay
X-ray

Software Mentioned

ImageJ
Fiji
ClustalW

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