Imperial College London
Alternate

DrJacquesBehmoaras

Faculty of Medicine, Department of Immunology and Inflammation

Reader in Immunogenetics
 
 
 
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Contact

 

+44 (0)20 3313 2339jacques.behmoaras Website

 
 
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Location

 

9N13Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Behmoaras:2020:10.1242/jcs.247957,
author = {Behmoaras, J and Ko, J-H and Olona, A and Papathanassiu, AE and Buang, N and Park, K-S and Costa, ASH and Mauro, C},
doi = {10.1242/jcs.247957},
journal = {Journal of Cell Science},
title = {BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages},
url = {http://dx.doi.org/10.1242/jcs.247957},
volume = {133},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - In response to environmental stimuli, macrophages change their nutrient consumption and undergo an early metabolic adaptation that progressively shapes their polarization state. During the transient, early phase of pro-inflammatory macrophage activation, an increase in tricarboxylic acid (TCA) cycle activity has been reported, but the relative contribution of branched-chain amino acid (BCAA) leucine remains to be determined. Here, we show that glucose but not glutamine is a major contributor of the increase in TCA cycle metabolites during early macrophage activation in humans. We then show that, although uptake of BCAAs is not altered, their transamination by BCAT1 is increased following 8h lipopolysaccharide (LPS) stimulation. Of note, leucine is not metabolized to integrate into the TCA cycle in basal or stimulated human macrophages. Surprisingly, the pharmacological inhibition of BCAT1 reduced glucose-derived itaconate, α-ketoglutarate and 2-hydroxyglutarate levels without affecting succinate and citrate levels, indicating a partial inhibition of the TCA cycle. This indirect effect is associated with NRF2 (also known as NFE2L2) activation and anti-oxidant responses. These results suggest a moonlighting role of BCAT1 through redox-mediated control of mitochondrial function during early macrophage activation.
AU  - Behmoaras,J
AU  - Ko,J-H
AU  - Olona,A
AU  - Papathanassiu,AE
AU  - Buang,N
AU  - Park,K-S
AU  - Costa,ASH
AU  - Mauro,C
DO  - 10.1242/jcs.247957
PY  - 2020///
SN  - 0021-9533
TI  - BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages
T2  - Journal of Cell Science
UR  - http://dx.doi.org/10.1242/jcs.247957
UR  - http://hdl.handle.net/10044/1/85078
VL  - 133
ER  -
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