Université Bourgogne Franche-Comté.
INSERM, LNC UMR1231.
Curr Opin Lipidol. 2022 Jun 1;33(3):193-198. doi: 10.1097/MOL.0000000000000820.
The turnover of fatty acids (FAs) at the sn-2 position of phospholipids is mediated by the reciprocal actions of phospholipases A2 and lyso-PL acyltransferases (LPLAT). LPCAT3, a major LPLAT isoform, exhibits a strong specificity for polyunsaturated FAs s (PUFAs). Although the enzyme was originally studied in the context of cardiometabolism, recent investigations have shed light on the role of LPCAT3 in other tissues such as skeletal muscle and in unexpected biological processes such as cell death and oncogenesis.
The three-dimensional structure of LPCAT3 has been elucidated allowing further understanding of the mechanism of the acylation reaction as well as the substrate specificity of the enzyme. In skeletal muscle, LPCAT3-mediated phospholipid remodeling modulates membrane domain clustering and insulin signalingLPCAT3 plays an important role in the process of ferroptosis by modulating the PUFA content of phospholipids and possibly of plasmalogens.In tumor-associated macrophages, LPCAT3 can prevent ER stress induced by the tumor microenvironment and may equally modulate antitumor immunity.
LPCAT3 is an attractive therapeutic target in the cardiometabolic disorders. Nevertheless, the involvement of LPCAT3 in processes such as cell death and oncogenesis demands caution with respect to the potential deleterious effects of enzyme modulation.
磷脂 sn-2 位脂肪酸（FAs）的周转是由磷脂酶 A2 和溶血磷脂酰基转移酶（LPLAT）的相互作用介导的。LPCAT3 是主要的 LPLAT 同工酶之一，对多不饱和脂肪酸（PUFAs）表现出很强的特异性。尽管该酶最初是在心脏代谢的背景下进行研究的，但最近的研究揭示了 LPCAT3 在其他组织（如骨骼肌）和意想不到的生物学过程（如细胞死亡和肿瘤发生）中的作用。
已经阐明了 LPCAT3 的三维结构，从而进一步了解酰化反应的机制以及酶的底物特异性。在骨骼肌中，LPCAT3 介导的磷脂重塑调节膜域聚类和胰岛素信号传导。LPCAT3 通过调节磷脂和可能的溶血磷脂的多不饱和脂肪酸含量，在铁死亡过程中发挥重要作用。在肿瘤相关巨噬细胞中，LPCAT3 可以防止肿瘤微环境引起的内质网应激，并可能同样调节抗肿瘤免疫。
LPCAT3 是心脏代谢紊乱的一个有吸引力的治疗靶点。然而，LPCAT3 参与细胞死亡和肿瘤发生等过程，需要谨慎对待酶调节的潜在有害影响。
