From the unfolded protein response to metabolic diseases – lipids under the spotlight
The unfolded protein response (UPR) is classically viewed as a stress response pathway to maintain protein homeostasis at the endoplasmic reticulum (ER). However, it has recently emerged that the UPR can be directly activated by lipid perturbation, independently of misfolded proteins. Comprising pri...
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| المؤلفون الرئيسيون: | , , |
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| مؤلفون آخرون: | |
| التنسيق: | مقال |
| اللغة: | English |
| منشور في: |
2018
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| الموضوعات: | |
| الوصول للمادة أونلاين: | https://hdl.handle.net/10356/87971 http://hdl.handle.net/10220/45592 |
| الوسوم: |
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| المؤسسة: | Nanyang Technological University |
| اللغة: | English |
| الملخص: | The unfolded protein response (UPR) is classically viewed as a stress response pathway to maintain protein homeostasis at the endoplasmic reticulum (ER). However, it has recently emerged that the UPR can be directly activated by lipid perturbation, independently of misfolded proteins. Comprising primarily phospholipids, sphingolipids and sterols, individual membranes can contain hundreds of distinct lipids. Even with such complexity, lipid distribution in a cell is tightly regulated by mechanisms that remain incompletely understood. It is therefore unsurprising that lipid dysregulation can be a key factor in disease development. Recent advances in analysis of lipids and their regulators have revealed remarkable mechanisms and connections to other cellular pathways including the UPR. In this Review, we summarize the current understanding in UPR transducers functioning as lipid sensors and the interplay between lipid metabolism and ER homeostasis in the context of metabolic diseases. We attempt to provide a framework consisting of a few key principles to integrate the different lines of evidence and explain this rather complicated mechanism. |
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