Raud 2016 Cell Metab
| Raud B, Roy DG, Divakaruni AS, Tarasenko TN, Franke R, Ma EH, Samborska B, Hsieh WY, Wong AH, Stüve P, Arnold-Schrauf C, Guderian M, Lochner M, Rampertaap S, Romito K, Monsale J, Brönstrup M, Bensinger SJ, Murphy AN, McGuire PJ, Jones RG, Sparwasser T, Berod L (2016) Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation. Cell Metab 28:504-515. |
Raud B, Roy DG, Divakaruni AS, Tarasenko TN, Franke R, Ma EH, Samborska B, Hsieh WY, Wong AH, Stüve P, Arnold-Schrauf C, Guderian M, Lochner M, Rampertaap S, Romito K, Monsale J, Brönstrup M, Bensinger SJ, Murphy AN, McGuire PJ, Jones RG, Sparwasser T, Berod L (2016) Cell Metab
Abstract: T cell subsets including effector (Teff), regulatory (Treg) and memory (Tmem) cells are characterized by distinct metabolic profiles that influence their differentiation and function. Previous research suggests that engagement of long-chain fatty acid oxidation (LC-FAO) supports Foxp3+ Treg cell and Tmem cell survival. However, evidence for this is mostly based on inhibition of Cpt1a, the rate limiting enzyme for LC-FAO, with the drug etomoxir. Using genetic models to target Cpt1a specifically in T cells, we dissected the role of LC-FAO in primary, memory and regulatory T cell responses. Here we show that the ACC2/Cpt1a axis is largely dispensable for Teff, Tmem or Treg cell formation, and that the effects of etomoxir on T cell differentiation and function are independent of Cpt1a expression. Together our data argue that metabolic pathways other than LC-FAO fuel Tmem or Treg differentiation and suggest alternative mechanisms for the effects of etomoxir that involve mitochondrial respiration.
Cited by
- Silva et al (2021) Off-target effect of etomoxir on mitochondrial Complex I. MitoFit Preprints 2021. (in preparation)
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MitoFit 2021 Etomoxir
