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).