9.B.164.  The TMEM164 Acyltransferase (TMEM164) Family 

Ferroptosis is an iron-dependent form of cell death driven by oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids. PUFA ether phospholipids (ePLs) promote ferroptosis. Reed et al. 2023 showed that TMEM164, the genetic ablation of which has been shown to protect cells from ferroptosis, is a cysteine active center enzyme that selectively transfers C20:4 acyl chains from phosphatidylcholine to lyso-ePLs to produce PUFA ePLs. Genetic deletion of TMEM164 across a set of ferroptosis-sensitive cancer cell lines caused selective reductions in C20:4 ePLs with minimal effects on C20:4 diacyl PLs, and this lipid profile produced protection from ferroptosis, suggesting a role for C20:4 ePLs in this form of cell death (Reed et al. 2023). It is also a transmembrane protein involved in shear stress signaling and hepatocarcinogenesis after a sustained virological response to hepatitis C virus (Nishikawa et al. 2023). Adeno-associated virus-mediated, astrocyte-specific TMEM164 overexpression in male and female mice prevents the induction of neurotoxic reactive astrocytes, dopaminergic neuronal loss and motor deficits in a Parkinson's disease model (Zhang et al. 2023).  TMEM164 may be  involved in the positive regulation of intramuscular fat deposition in pectoralis (Wang et al. 2023).


 

References:

Liu, J., Y. Liu, Y. Wang, C. Li, Y. Xie, D.J. Klionsky, R. Kang, and D. Tang. (2023). TMEM164 is a new determinant of autophagy-dependent ferroptosis. Autophagy 19: 945-956.
Nishikawa, M., H. Okada, K. Kawaguchi, T. Shimakami, K. Nio, K. Arai, T. Yamashita, M. Sasaki, S. Kaneko, T. Yamashita, and M. Honda. (2023). Identification of a Transmembrane Protein Involved in Shear Stress Signaling and Hepatocarcinogenesis After a Sustained Virological Response to Hepatitis C Virus. Cell Mol Gastroenterol Hepatol 16: 263-286.
Reed, A., T. Ware, H. Li, J. Fernando Bazan, and B.F. Cravatt. (2023). TMEM164 is an acyltransferase that forms ferroptotic C20:4 ether phospholipids. Nat Chem Biol 19: 378-388.
Wang, D., P. Qin, K. Zhang, Y. Wang, Y. Guo, Z. Cheng, Z. Li, Y. Tian, X. Kang, H. Li, and X. Liu. (2023). Integrated LC/MS-based lipidomics and transcriptomics analyses revealed lipid composition heterogeneity between pectoralis intramuscular fat and abdominal fat and its regulatory mechanism in chicken. Food Res Int 172: 113083.
Zhang, L., Z. Jia, Q. Wu, T. Bai, B. Wang, X. Hu, T. Li, X. Liu, J. Fu, Y. Chen, X. Ding, Z. Liu, Z. Xu, and H. Zhou. (2023). Alleviating symptoms of neurodegenerative disorders by astrocyte-specific overexpression of TMEM164 in mice. Nat Metab. [Epub: Ahead of Print]
Examples:

TC#NameOrganismal TypeExample
9.B.457.1.1

TMEM164 of 297 aas and 7 TMSs in a 1 + 5 + 1 TMS arrangement.  See family description for details (Liu et al. 2023).

TMEM164 of Homo sapiens

 
9.B.457.1.2

TMEM164 of 322 aas and 7 TMSs in a 1 + 4 + 1 + 1 TMS arrangement.  TMEM164 in chicken might be involved in the positive regulation of intramuscular fat deposition in pectoralis (Wang et al. 2023).

TMEM164 of Gallus gallus (chicken)

 
9.B.457.1.3

TMEM164 protein of 303 aas and 7 TMSs in a 1 + 4 + 1 + 1 TMS arrangement.

TMEM164 of Thamnidium elegans

 
9.B.457.1.4

TMEM164 family protein of 303 aas and 7 TMSs in a 1 + 4 + 2 TMS arrangement.

TMEM164 of Nitzschia inconspicua

 
9.B.457.1.6

Uncharacterized protein of 302 aas and 7 TMSs in a 1 + 5 + 1 TMS arrangement.

UP of Acanthamoeba castellanii