PAQR proteins and the evolution of a superpower: Eating all kinds of fats

Abstract

Recently published work showed that members of the PAQR protein family are activated by cell membrane rigidity and contribute to our ability to eat a wide variety of diets. Cell membranes are primarily composed of phospholipids containing dietarily obtained fatty acids, which poses a challenge to membrane properties because diets can vary greatly in their fatty acid composition and could impart opposite properties to the cellular membranes. In particular, saturated fatty acids (SFAs) can pack tightly and form rigid membranes (like butter at room temperature) while unsaturated fatty acids (UFAs) form more fluid membranes (like vegetable oils). Proteins of the PAQR protein family, characterized by the presence of seven transmembrane domains and a cytosolic N‐terminus, contribute to membrane homeostasis in bacteria, yeasts, and animals. These proteins respond to membrane rigidity by stimulating fatty acid desaturation and incorporation of UFAs into phospholipids and explain the ability of animals to thrive on diets with widely varied fat composition.

Aging AdipoR2‐deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids

“…53 AdipoR2 is an evolutionarily conserved multi-pass transmembrane protein required for membrane composition homeostasis (reviewed in Refs. [54,55]). Mechanistically, decreased membrane fluidity activates a ceramidase activity intrinsic to AdipoR2 that results in the production of the signaling molecule sphingosine 1-phosphate that in turn activates transcription factors driving desaturase expression.…”