O'Connor 2018 Sci Rep
| O'Connor RS, Guo L, Ghassemi S, Snyder NW, Worth AJ, Weng L, Yoonseok Kam Y, Philipson B, Trefely S, Nunez-Cruz S, Blair IA, June CH, Milone MC (2018) The CPT1a inhibitor, etomoxir induces severe oxidative stress at commonly used concentrations. Sci Rep 8:6289. |
O'Connor RS, Guo L, Ghassemi S, Snyder NW, Worth AJ, Weng L, Yoonseok Kam Y, Philipson B, Trefely S, Nunez-Cruz S, Blair IA, June CH, Milone MC (2018) Sci Rep
Abstract: Etomoxir (ETO) is a widely used small-molecule inhibitor of fatty acid oxidation (FAO) through its irreversible inhibitory effects on the carnitine palmitoyl-transferase 1a (CPT1a). We used this compound to evaluate the role of fatty acid oxidation in rapidly proliferating T cells following costimulation through the CD28 receptor. We show that ETO has a moderate effect on T cell proliferation with no observable effect on memory differentiation, but a marked effect on oxidative metabolism. We show that this oxidative metabolism is primarily dependent upon glutamine rather than FAO. Using an shRNA approach to reduce CPT1a in T cells, we further demonstrate that the inhibition of oxidative metabolism in T cells by ETO is independent of its effects on FAO at concentrations exceeding 5โฮผM. Concentrations of ETO above 5โฮผM induce acute production of ROS with associated evidence of severe oxidative stress in proliferating T cells. In aggregate, these data indicate that ETO lacks specificity for CTP1a above 5โฮผM, and caution should be used when employing this compound for studies in cells due to its non-specific effects on oxidative metabolism and cellular redox.
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
