Endoplasmic Reticulum Stress and Metabolic Dysfunction

Abstract: In eukaryotic cells， the endoplasmic reticulum (ER) is a crucial site for protein synthesis， folding and quality control. Increased workload of protein folding during ER stress triggers the cellular unfolded protein response (UPR)， and failure of the ER to adapt to ER stress leads to cellular dysfunction and apoptosis. The ERlocalized transmembrane proteins ATF6， PERK and IRE1 mediate the three canonical branches of the UPR signaling pathways， which coordinately enhance the functional folding capacity of the ER to manage ER stress. Thus， the UPR is of central importance to cellular homeostasis and survival. Emerging evidence has shown that the UPR pathways are closely associated with cellular nutrient-sensing mechanisms as well as glucose and lipid metabolism. ER stress is found to affect key regulatory programs in metabolically active organs including the liver， adipose tissues， pancreatic islets and hypothalamus， and it is increasingly recognized as a critical player in the derangement of metabolic homeostasis. Thus， a better understanding of the pathogenic role of the ER stress pathways will offer novel targets for developing therapeutic leads against metabolic diseases such as obesity and type 2 diabetes.

CSTR: 32200.14.cjcb.2011.07.0001