Endoplasmic reticulum architecture in liver metabolic regulation

The endoplasmic reticulum (ER) is a central hub for essential cellular processes, including lipid and glucose metabolism, protein folding, calcium homeostasis, and detoxification. The ER exhibits a complex architecture, comprising multiple subdomains such as the nuclear envelope and the peripheral ER, which is further organized into sheets, tubules, three-way junctions, and contact sites. Both ER form and function are highly adaptive, with a robust capacity to respond to changes in environmental cues such as nutritional states. Here, we discuss remodeling of ER shape - as a fundamental mechanism of metabolic regulation, which enables the diversification and fine-tuning of metabolic function in physiology, while also representing a potential point of vulnerability during metabolic stress. We focus on the liver, a central organ in systemic energy homeostasis, and examine how hepatic ER morphology and its dynamic interorganelle interactions are reorganized in response to nutritional fluctuations and how this remodeling reflects on metabolic function.