| First Author | Kitai Y | Year | 2013 |
| Journal | Genes Cells | Volume | 18 |
| Issue | 9 | Pages | 798-809 |
| PubMed ID | 23803178 | Mgi Jnum | J:214026 |
| Mgi Id | MGI:5587881 | Doi | 10.1111/gtc.12074 |
| Citation | Kitai Y, et al. (2013) Membrane lipid saturation activates IRE1alpha without inducing clustering. Genes Cells 18(9):798-809 |
| abstractText | The unfolded protein response (UPR) is an adaptive stress response that responds to the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) and that adjusts the protein-folding capacity to the needs of the cell. Perturbation of cellular lipids also activates the UPR. Lipid-induced UPR has attracted much attention because it is associated with the pathology of some metabolic diseases. However, how the lipid-induced UPR is activated remains unclear. We previously showed that palmitic acid treatment or knockdown of stearoyl-CoA desaturase in HeLa cells promotes membrane lipid saturation and activates the UPR. In this study, we compared UPR activation by membrane lipid saturation with UPR activation by conventional ER stressors that cause the accumulation of unfolded proteins such as tunicamycin and thapsigargin. Membrane lipid saturation induced autophosphorylation of inositol-requiring 1alpha (IRE1alpha) and protein kinase RNA-like ER kinase, but not the conversion of activating transcription factor-6alpha to the active form. A conventional ER stressor induced clustering of fluorescently tagged IRE1alpha fusion protein, but palmitic acid treatment did not, suggesting that IRE1alpha was activated without large cluster formation by membrane lipid saturation. Together, these results suggest membrane lipid saturation, and unfolded proteins activate the UPR through different mechanisms. |
