在受损后,ATXN3通过准K48-K63-分支的泛素链来调节 lysosome 的再生
Maike Reinders1, Bojana Kravic1, Pinki Gahlot1
1Molecular Biology I, Center of Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen, Germany.
The EMBO journal
|July 29, 2025
概括
双化酶ATXN3通过去除特定的化链来修复受损的溶酶,有助于再生和恢复细胞功能. 这一过程对溶酶体健康和细胞应激反应至关重要.
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:
- 细胞损伤反应涉及溶酶体的修复,再生和溶酶体.
- 这些溶酶体损伤反应机制的协调仍然不清楚.
研究的目的:
- 为了研究二基化酶ATXN3在 lysosomal损伤反应中的作用.
- 阐明 lysosomal 修复,再生和 lysophagy 之间的协调.
主要方法:
- lysosomal损伤的人类细胞模型.
- 免疫光显微镜用于追踪ATXN3局部化和无素链修饰.
- 生物化学测试以评估溶酶体再酸化和降解能力.
- lysophagic流和微自的分析.
主要成果:
- ATXN3的目标是K48-K63分支的泛素链在再生的溶酶体上.
- ATXN3被招募到特定的溶解体中,这些溶解体标记为酸丁酸-4,5) - 双酸盐和不完全的重新酸化.
- 具有VCP/p97的ATXN3促进LAMP2的微自,用于膜再生.
- ATXN3对于溶解体流的完成是必不可少的,但不是初始的光体形成.
结论:
- 在膜损伤后,ATXN3在恢复 lysosomal 完整性和功能方面发挥着至关重要的作用.
- K48-K63分支的乌比奎丁链循环调节了溶酶体的再生.
- 这项研究揭示了一种新的溶酶体损伤反应机制,涉及ATXN3介导的再生和微自.
相关概念视频
Regulated Protein Degradation
7.6K
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...
7.6K
Delivery Pathways to the Lysosome
7.2K
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...
7.2K
The Proteasome
1.2K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.2K
Lysosomal Hydrolases
3.9K
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,...
3.9K
Autophagy
4.6K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.6K
Export of Misfolded Proteins out of the ER
3.9K
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...
3.9K


