Premium
Lipid biosynthesis and the unfolded protein response
Author(s) -
Bommiasamy Hemamalini,
Sriburi Rungtawan,
Fagone Paolo,
Jackowski Suzanne,
Brewer Joseph W.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1034.3
Subject(s) - unfolded protein response , atf6 , endoplasmic reticulum , microbiology and biotechnology , biogenesis , phospholipid , peroxisome , chemistry , lipid droplet , lipid metabolism , protein biosynthesis , biochemistry , secretory protein , transcription factor , biology , secretion , gene , membrane
Professional secretory cells possess an expansive endoplasmic reticulum (ER) to accommodate high‐rate protein production. ER biogenesis requires phospholipids and phospholipid synthesis requires fatty acids. Yet, the mechanisms that regulate phospholipid and fatty acid supply when demand for ER increases are incompletely understood. A link exists between ER expansion and the unfolded protein response (UPR), a stress‐induced signaling pathway that emanates from the ER. The UPR transcriptional activator XBP‐1(S) is required for proper ER development in specialized secretory cells and is sufficient upon overexpression to induce phospholipid synthesis and ER expansion. We find that enforced expression of ATF6, another UPR transcription factor, upregulates phospholipid synthesis and ER biogenesis in fibroblasts. Furthermore, enforced expression of either XBP‐1(S) or ATF6 results in increased fatty acid biosynthesis. Interestingly, fibroblasts overexpressing either XBP‐1(S) or ATF6 differ in their expression of lipid metabolic genes, suggesting that these two UPR factors have the capacity to regulate lipid and fatty acid biosynthesis by distinct mechanisms. These studies reveal further complexity in the relationship between the UPR, lipid production and ER biogenesis. [supported by NIH Grants GM 61970 (J.W.B.), GM 45737 (S.J.), T32 AI007508 (H. B.) and by ALSAC]