As a matter of fat: Emerging roles of lipid-sensitive E3 ubiquitin ligases

The dynamic structure and composition of lipid membranes need to be tightly regulated to control the vast array of cellular processes from cell and organelle morphology to protein-protein interactions and signal transduction pathways. To maintain membrane integrity, sense-and-response systems monitor and adjust membrane lipid composition to the ever-changing cellular environment, but only a relatively small number of control systems have been described. Here, we explore the emerging role of the ubiquitin-proteasome system in monitoring and maintaining membrane lipid composition. We focus on the ER-resident RNF145 E3 ubiquitin ligase, its role in regulating adiponectin receptor 2 (ADIPOR2), its lipid hydrolase substrate, and the broader implications for understanding the homeostatic processes that fine-tune cellular membrane composition. Lipids are essential components of cellular membranes. E3 ubiquitin ligases are emerging as important regulators of lipid homeostasis of cell membranes. E3s involved in responding to changes in sterols levels and lipid saturation detect and directly act to adapt to these changes in membrane properties. image