The expanding role of lyso-phosphatidylcholine acyltransferase-3 (LPCAT3), a phospholipid remodeling enzyme, in health and disease

Purpose of review 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. Recent findings 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 signaling LPCAT3 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.

Automated summary

LPCAT3, a major lysophosphatidylcholine acyltransferase isoform, has been studied extensively in the context of cardiometabolism. Recent investigations have expanded the understanding of LPCAT3's role in other tissues such as skeletal muscle and in unexpected biological processes such as cell death and oncogenesis. The elucidation of LPCAT3's three-dimensional structure has provided further insight into the enzyme's mechanism and substrate specificity. LPCAT3 plays a critical role in skeletal muscle membrane remodeling, insulin signaling, and the process of ferroptosis. Additionally, LPCAT3 may modulate ER stress and antitumor immunity in tumor-associated macrophages. However, caution is needed in targeting LPCAT3 due to the potential deleterious effects on cell death and oncogenesis.