与ER相关的降解与lysosome相关的降解
1Università della Svizzera italiana, Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland; School of Life Sciences, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Current biology : CB
|May 6, 2025
概括
毛里齐奥·莫利纳里 (Maurizio Molinari) 解释了ER-to-lysosome相关降解,这是一种涉及自和非自途径的过程. 这种机制降解了抵抗ER相关降解的错误折叠蛋白质,维持细胞蛋白质稳定.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞蛋白质稳定依赖于高效的蛋白质降解途径.
- 错误折叠的蛋白质积聚在内质网膜 (ER) 中,对细胞健康构成威胁.
- 与ER相关的降解 (ERAD) 针对错误折叠的蛋白质,但可以被压倒.
研究的目的:
- 引入和定义ER-至-溶酶体相关降解 (ERLAD).
- 阐明ERLAD所涉及的自和非自途径.
- 突出ERLAD在降解ERAD抗性错折蛋白中的作用.
主要方法:
- 对有关蛋白质降解和 lysosomal 途径的现有文献的审查.
- 了解ERLAD路径的概念框架.
- 整合关于ER质量控制和 lysosomal 功能的知识.
主要成果:
- ERLAD包括不同的自和非自路线.
- 这些通路特别针对错误折叠的蛋白质,这些蛋白质逃避了传统的ERAD.
- 埃拉德将这些蛋白质送到 lysosome 中进行降解.
结论:
- ERLAD是维持蛋白质稳定性的关键细胞机制.
- 它为ERAD提供了一个补充的途径,用于清除有问题的蛋白质.
- 了解ERLAD对于理解细胞对压力和疾病的反应至关重要.
相关概念视频
Export of Misfolded Proteins out of the ER
3.3K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.3K
Lysosomes
13.5K
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
13.5K
Delivery Pathways to the Lysosome
6.1K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.1K
ER Retrieval Pathway
3.6K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.6K
Lysosomal Hydrolases
3.7K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.7K
Regulated Protein Degradation
7.1K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.1K


