脂质平衡对于最大的ER应激反应至关重要
Gilberto Garcia1,2, Hanlin Zhang1, Sophia Moreno1
1Department of Molecular & Cellular Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States.
eLife
|July 25, 2023
概括
莱特-767基因影响脂质储存和内质网膜 (ER) 蛋白质稳态. 改变的脂质代谢会影响ER.
科学领域:
- 细胞生物学 细胞生物学
- 代谢研究 研究 代谢研究
- 老龄化和疾病研究研究.
背景情况:
- 脂质代谢的变化与衰老和诸如蛋白质病变等疾病有关.
- 细胞内膜网膜 (ER) 对于蛋白质和脂质平衡至关重要.
- 脂质代谢和蛋白质质量控制之间的相互作用尚未完全理解.
研究的目的:
- 为了研究let-767基因在脂质和ER蛋白质平衡中的作用.
- 阐明脂质代谢与ER (UPRER) 的未折叠蛋白质反应之间的联系.
主要方法:
- 鉴定了let-767作为*Caenorhabditis elegans*的一个关键基因.
- 分析了let-767敲击对脂质储存和ER形态学的影响.
- 研究了脂质代谢调节对UPRER诱导的影响.
主要成果:
- 让-767敲击降低了脂质储存,并以脂质依赖的方式改变了ER形态.
- let-767敲击阻断了ER (UPRER) 的未折叠蛋白反应的诱导.
- 减少脂质性通路或补充3-oxoacyl恢复的UPRER诱导在让-767敲击动物.
结论:
- let-767对于维持脂质和ER蛋白质均适应性至关重要.
- 脂质代谢直接影响细胞对ER蛋白应激反应的反应.
- 这项研究揭示了一种新的机制,将脂质代谢与蛋白质质量控制联系起来.
相关概念视频
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Assembly of the Lipid Bilayer in the ER
3.2K
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
3.2K
Role of ER in the Secretory Pathway
5.5K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.5K
Smooth Endoplasmic Reticulum
5.8K
Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
5.8K
The Endoplasmic Reticulum
14.9K
The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
14.9K


