ACSL3 (human, recombinant; aa 45-720)

Long-chain acyl-CoA synthetase 3 (ACSL3) is an enzyme involved in lipid biosynthesis and fatty acid degradation.¹ It is composed of short N- and C-terminal domains surrounding an AMP-binding domain.² It is expressed in the brain and prostate and localizes to the endoplasmic reticulum, mitochondria, and lipid droplets.¹ ACSL3 is activated by a variety of factors, including peroxisome proliferator-activated receptor δ (PPARδ), octamer-binding transcription factor 1 (Oct1), and the liver X receptor (LXR), among others. ACSL3 converts free monounsaturated long-chain fatty acids into fatty acyl-CoA esters, which are used as substrates for phospholipid and glycerolipid biosynthesis or transported into the mitochondria to be degraded via fatty acid β-oxidation for use as an energy source.^1,3,4 ACSL3-dependent conversion of exogenous MUFAs into fatty acyl-CoA esters can induce resistance to ferroptotic cell death by displacing PUFAs and preventing the accumulation of lipid reactive oxygen species (ROS) in the plasma membrane.^3,5 ACSL3 is required for tumor cell survival in non-small cell lung cancer (NSCLC) mouse xenograft models, including those expressing K-Ras containing the glycine-to-aspartate activating mutation at position 12 (K-Ras^G12D).⁶ It is also highly expressed in tumor tissues isolated from patients with early-stage NSCLC. In contrast, homozygous deletion of ACSL3 is associated with an increased risk of metastasis or recurrence in patients with triple-negative breast cancer (TNBC) receiving adjuvant chemotherapy.⁷ Cayman’s ACSL3 (human, recombinant; aa 45-720) protein can be used for ELISA, enzyme activity assay, and Western blot applications.

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1. Quan, J., Bode, A.M., and Luo, X. ACSL family: The regulatory mechanisms and therapeutic implications in cancer. Eur. J. Pharmacol. 909, 174397 (2021).

2. Poppelreuther, M., Rudolph, B., Du, C., et al. The N-terminal region of acyl-CoA synthetase 3 is essential for both the localization on lipid droplets and the function in fatty acid uptake. J. Lipid Res. 53(5), 888-900 (2012).

3. Dixon, S.J., and Olzmann, J.A. The cell biology of ferroptosis. Nat. Rev. Mol. Cell Biol. (2024).

4. Yang, Y., Zhu, T., Wang, X., et al. ACSL3 and ACSL4, distinct roles in ferroptosis and cancers. Cancers (Basel) 14(23), 5896 (2022).

5. Magtanong, L., Ko, P.-J., To, M., et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem. Biol. 26(3), 420-432 (2019).

6. Padanad, M.S., Konstantinidou, G., Venkateswaran, N., et al. Fatty acid oxidation mediated by acyl-CoA synthetase long chain 3 is required for mutant KRAS lung tumorigenesis. Cell Rep. 16(6), 1614-1628 (2016).

7. Jeong, H.M., Kim, R.N., Kwon, M.J., et al. Targeted exome sequencing of Korean triple-negative breast cancer reveals homozygous deletions associated with poor prognosis of adjuvant chemotherapy-treated patients. Oncotarget 8(37), 61538-61550 (2017).