Lipoquality control by phospholipase A₂ enzymes

The phospholipase A₂ (PLA₂) family comprises a group of lipolytic enzymes that typically hydrolyze the sn-2 position of glycerophospholipids to give rise to fatty acids and lysophospholipids. The mammalian genome encodes more than 50 PLA₂s or related enzymes, which are classified into several subfamilies on the basis of their structures and functions. From a general viewpoint, the PLA₂ family has mainly been implicated in signal transduction, producing bioactive lipid mediators derived from fatty acids and lysophospholipids. Recent evidence indicates that PLA₂s also contribute to phospholipid remodeling for membrane homeostasis or energy production for fatty acid β-oxidation. Accordingly, PLA₂ enzymes can be regarded as one of the key regulators of the quality of lipids, which I herein refer to as lipoquality. Disturbance of PLA₂-regulated lipoquality hampers tissue and cellular homeostasis and can be linked to various diseases. Here I overview the current state of understanding of the classification, enzymatic properties, and physiological functions of the PLA₂ family.