Ech1, also known as enoyl-CoA hydratase 1, is a key enzyme in mitochondrial fatty acid β-oxidation. It catalyzes the isomerization of unsaturated fatty acids (UFAs), and is involved in lipid metabolism-related pathways. Its biological importance extends to various physiological and pathological processes [3,4,5,7]. Genetic models, such as KO/CKO mouse models, can be valuable for studying its functions.

In the context of cancer, downregulation of Ech1 in Hca-F cells inhibited their metastatic capability to peripheral lymph nodes in vivo, indicating that Ech1 may be a suppressor of lymphatic metastasis in hepatocarcinoma [2]. In ovarian cancer metastasis, high polyunsaturated fatty acyl (PUFA)-lipid state created by acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) makes cancer cells dependent on Ech1, as it is a rate-limiting enzyme preparing UFAs for β-oxidation. Co-inhibition of ACSL4/Ech1 potently suppressed metastasis [1]. In glioblastoma, TNF receptor-associated factor 3 (TRAF3) interacts with Ech1 and mediates its K63-linked ubiquitination at Lys214, which impedes TOMM20-dependent mitochondrial translocation of Ech1, affecting the oxidation of UFAs and lipid peroxidation [3].

In summary, Ech1 plays a crucial role in lipid metabolism-related biological processes. Its functions are revealed through in vivo studies, especially in mouse models. In cancer, it shows potential as a therapeutic target for metastasis and in glioblastoma for regulating lipid peroxidation and immune elimination. In other diseases like non-alcoholic steatohepatitis, aortic valve calcification, and atherosclerosis, Ech1 also demonstrates protective effects through various mechanisms related to its role in lipid metabolism [4,5,6].

References:

1. Wang, Yuqi, Hu, Mangze, Cao, Jian, Wang, Xi, Zou, Yilong. 2024. ACSL4 and polyunsaturated lipids support metastatic extravasation and colonization. In Cell, 188, 412-429.e27. doi:10.1016/j.cell.2024.10.047. https://pubmed.ncbi.nlm.nih.gov/39591965/

2. Zhang, Jun, Sun, Mingzhong, Li, Rongkuan, Ibrahim, Mohammed Mohammed, Tang, Jianwu. 2013. Ech1 is a potent suppressor of lymphatic metastasis in hepatocarcinoma. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 67, 557-60. doi:10.1016/j.biopha.2013.03.018. https://pubmed.ncbi.nlm.nih.gov/23809371/

3. Zeng, Yu, Zhao, Liqian, Zeng, Kunlin, Song, Ye, Zhou, Aidong. 2025. TRAF3 loss protects glioblastoma cells from lipid peroxidation and immune elimination via dysregulated lipid metabolism. In The Journal of clinical investigation, 135, . doi:10.1172/JCI178550. https://pubmed.ncbi.nlm.nih.gov/39932808/

4. Rao, Caijun, Liu, Baoqing, Qin, Haojie, Du, Zhipeng. 2024. Enoyl coenzyme a hydratase 1 attenuates aortic valve calcification by suppressing Runx2 via Wnt5a/Ca2+ pathway. In Journal of cell communication and signaling, 18, e12038. doi:10.1002/ccs3.12038. https://pubmed.ncbi.nlm.nih.gov/38946717/

5. Liu, Bing, Yi, Wei, Mao, Xiaoxiang, Yang, Ling, Rao, Caijun. 2021. Enoyl coenzyme A hydratase 1 alleviates nonalcoholic steatohepatitis in mice by suppressing hepatic ferroptosis. In American journal of physiology. Endocrinology and metabolism, 320, E925-E937. doi:10.1152/ajpendo.00614.2020. https://pubmed.ncbi.nlm.nih.gov/33813878/

6. Rao, Caijun, Qin, Haojie, Du, Zhipeng. 2024. ECH 1 attenuates atherosclerosis by reducing macrophage infiltration and improving plaque stability through CD36 degradation. In Archives of biochemistry and biophysics, 763, 110217. doi:10.1016/j.abb.2024.110217. https://pubmed.ncbi.nlm.nih.gov/39551333/

7. Huang, Dandan, Liu, Baoqing, Huang, Kai, Huang, Kun. 2018. Enoyl coenzyme A hydratase 1 protects against high-fat-diet-induced hepatic steatosis and insulin resistance. In Biochemical and biophysical research communications, 499, 403-409. doi:10.1016/j.bbrc.2018.03.052. https://pubmed.ncbi.nlm.nih.gov/29526751/