Endoplasmic Reticulum-Associated Degradation and Lipid Homeostasis.
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.
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720; email: olzmann@berkeley.edu.
Julian
J
Stevenson
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720; email: olzmann@berkeley.edu.
Edmond Y
EY
Huang
Program in Metabolic Biology, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720; email: olzmann@berkeley.edu.
James A
JA
Olzmann
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008954:Models, Biological; D014176:Protein Biosynthesis; D017510:Protein Folding; D055550:Protein Stability; D055571:Secretory Pathway; D014280:Triglycerides / Q000378:metabolism
D008074:Lipoproteins; D014280:Triglycerides; D002784:Cholesterol
ERAD; cholesterol; lipid droplet; quality control; triacylglycerol; ubiquitin