同类氨酸通过抑制V-ATPase来破坏 lysosomal 功能
Yang Yang1,2, Qianjin Kong1,2, Chaolian Liu1
1Yunnan Key Laboratory of Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, Yunnan University , Kunming, China.
The Journal of cell biology
|November 25, 2025
概括
有害的代谢物同型氨酸通过抑制V-ATPase来损害 lysosomes,导致 lysosomal 功能障碍和储存疾病. 这项研究揭示了 homocystinuria 发病的关键机制.
科学领域:
- 细胞生物学 细胞生物学
- 代谢障碍 代谢障碍 代谢障碍
- 生物化学 生物化学
背景情况:
- 溶解体对于代谢平衡和细胞信号传递至关重要.
- 有害代谢物在代谢疾病中的溶酶体功能障碍中的作用尚不清楚.
研究的目的:
- 为了研究同类氨酸,一种与同类氨酸尿症相关的代谢物,如何影响 lysosome 功能.
- 为了阐明背后的分子机制同类氨酸诱导的 lysosomal 损伤.
主要方法:
- 使用了Caenorhabditis elegans和小鼠模型.
- 分析了对溶酶体V-ATPase活性和溶酶体形态学产生的同类半氨酸积累的影响.
- 研究了V-ATPase的同类氨酸结合和同类氨酸inylation.
主要成果:
- 由囊氨酸β-合成酶缺乏引起的homocysteine积累导致C. elegans的发育停止.
- 同类氨酸直接通过结合和同类氨基酶来抑制V-ATPase,从而损害了 lysosomal 降解.
- 在C. elegans和Cbs缺乏的小鼠中观察到扩大的溶解体与载荷积累和膜损伤,类似于溶解体储存疾病.
结论:
- 代谢物同型氨酸通过抑制V-ATPase直接损害 lysosomes.
- lysosomal 损伤是 homocystinuria 和相关代谢障碍病理学的关键因素.
- 这项研究为代谢物诱导的器官损伤和疾病机制提供了新的见解.
更多相关视频
09:51Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
Published on: June 30, 2023
1.4K
11:12Ex Vivo Red Blood Cell Hemolysis Assay for the Evaluation of pH-responsive Endosomolytic Agents for Cytosolic Delivery of Biomacromolecular Drugs
Published on: March 9, 2013
35.5K
相关概念视频
01:22Lysosomal Hydrolases
4.4K
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,...
4.4K
01:36Delivery Pathways to the Lysosome
8.7K
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...
8.7K
01:31Lysosomes
25.2K
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,...
25.2K
01:13The Proteasome
1.6K
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...
1.6K
02:18The Proteasome
10.0K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst 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. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.0K
01:19Allosteric Proteins-ATCase
6.4K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.4K