The PLAAT family as phospholipid-related enzymes

Abstract

The phospholipase A and acyltransferase (PLAAT) family is a group of structurally related proteins that are conserved among vertebrates. In humans, the family comprises five members (PLAAT1–5), which share common domain structures, and functions as phospholipase A₁/A₂ and acyltransferase enzymes. Regarding acyltransferase activities, PLAATs produce N-acyl-phosphatidylethanolamines, which serve as the precursor of bioactive N-acylethanolamines (NAEs). Recent evidence strongly suggests that PLAAT proteins play a crucial role in maintaining homeostasis in various organelles, such as the endoplasmic reticulum, lysosomes, mitochondria, and peroxisomes. In this process, PLAAT proteins bind to organelles and degrade them in an enzyme activity-dependent manner. Their physiological significance was revealed by the inability of PLAAT-deficient animals to degrade organelles during the maturation of the eye lens, resulting in the development of cataracts. Furthermore, the deficiency of PLAAT1, 3, and 5 in mice caused resistance to high-fat diet-induced fatty liver, the lean phenotype represented by a marked decrease in adipose tissue mass, and the exacerbation of testicular inflammation due to decreased levels of anti-inflammatory NAEs, respectively. In addition, human PLAAT3 was identified as a causative gene for lipodystrophy. We herein provide an overview of the molecular and biological properties of PLAAT proteins.