Stevenson Julian, Huang Edmond Y, Olzmann James A
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720; email:
Annu Rev Nutr. 2016 Jul 17;36:511-42. doi: 10.1146/annurev-nutr-071715-051030. Epub 2016 May 26.
The endoplasmic reticulum is the port of entry for proteins into the secretory pathway and the site of synthesis for several important lipids, including cholesterol, triacylglycerol, and phospholipids. Protein production within the endoplasmic reticulum is tightly regulated by a cohort of resident machinery that coordinates the folding, modification, and deployment of secreted and integral membrane proteins. Proteins failing to attain their native conformation are degraded through the endoplasmic reticulum-associated degradation (ERAD) pathway via a series of tightly coupled steps: substrate recognition, dislocation, and ubiquitin-dependent proteasomal destruction. The same ERAD machinery also controls the flux through various metabolic pathways by coupling the turnover of metabolic enzymes to the levels of key metabolites. We review the current understanding and biological significance of ERAD-mediated regulation of lipid metabolism in mammalian cells.
内质网是蛋白质进入分泌途径的入口，也是几种重要脂质（包括胆固醇、三酰甘油和磷脂）的合成场所。内质网内的蛋白质生产受到一组驻留机制的严格调控，这些机制协调分泌蛋白和整合膜蛋白的折叠、修饰和转运。未能达到天然构象的蛋白质通过内质网相关降解（ERAD）途径，经过一系列紧密耦合的步骤被降解：底物识别、错位和泛素依赖性蛋白酶体破坏。同样的ERAD机制还通过将代谢酶的周转与关键代谢物的水平相耦合，来控制各种代谢途径的通量。我们综述了目前对哺乳动物细胞中ERAD介导的脂质代谢调控的理解及其生物学意义。
