title: The role of phospholipids in the biological activity and structure of the endoplasmic reticulum.
abstract: The endoplasmic reticulum (ER) is an interconnected network of tubular and planar membranes that supports the synthesis and export of proteins, carbohydrates and lipids. Phospholipids, in particular phosphatidylcholine (PC), are synthesized in the ER where they have essential functions including provision of membranes required for protein synthesis and export, cholesterol homeostasis, and triacylglycerol storage and secretion. Coordination of these biological processes is essential, as highlighted by findings that link phospholipid metabolism in the ER with perturbations in lipid storage/secretion and stress responses, ultimately contributing to obesity/diabetes, atherosclerosis and neurological disorders. Phospholipid synthesis is not uniformly distributed in the ER but is localized at membrane interfaces or contact zones with other organelles, and in dynamic, proliferating ER membranes. The topology of phospholipid synthesis is an important consideration when establishing the etiology of diseases that arise from ER dysfunction. This review will highlight our current understanding of the contribution of phospholipid synthesis to proper ER function, and how alterations contribute to aberrant stress responses and disease. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada. tlagace@ottawaheart.ca
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Lagace
authors.forename: Neale D
authors.initials: ND
authors.lastname: Ridgway
mesh_terms: D000818:Animals; D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D010743:Phospholipids
keywords: AGPAT; ATF6; C/EBP homologous protein; CCT; CDP-DAG synthase; CDP-choline (ethanolamine): diacylglycerol choline (choline/ethanolamine) phosphotransferases; CDS; CHOP; CPT/CEPT; CTP:phosphocholine cytidylyltransferase; Cholesterol; DAG; DGAT; ER; ERMES; ER–mitochondrial encounter structure; GPAT; IRE1; LD; MAM; Membranes; NR; PA; PC; PE; PEMT; PERK; PI; PIS; PKR-like eukaryotic initiation factor 2a kinase; PLA(2); PS; Phosphatidylcholine; Phospholipids; SCAP; SCD1; SERCA; SREBP; SREBP cleavage-activating protein; TAG; UPR; VLDL; X-box binding proten-1; XBP-1; activating transcription factor-6; acylglycerolphosphate acyltransferase; diacylglycerol; diacylglycerol acyltransferase; endoplasmic reticulum; glycerol 3-phosphate acyltransferase; inositol requiring enzyme 1; lipid droplet; mitochondrial-associated membrane; nucleoplasmic reticulum; phosphatidic acid; phosphatidylcholine; phosphatidylethanolamine; phosphatidylethanolamine N-methyltransferase; phosphatidylinositol; phosphatidylinositol synthase; phosphatidylserine; phospholipase A2; sarco/endoplasmic reticulum calcium-ATPase; stearoyl-CoA desaturase-1; sterol regulatory-element binding protein; triacylglycerol; unfolded protein response; very low-density lipoprotein