溶酶体的机械弹性是由TMEM63A赋予的
Angelina S Kim1,2, Jing Ze Wu1,2, Ruiqi Cai1,2
1Program in Cell and Systems Biology, SickKids Research Institute , Toronto, Canada.
The Journal of cell biology
|March 11, 2026
概括
溶解体可以通过TMEM63A通道感知和缓解膜张力,防止破裂. 缺乏功能性TMEM63A的细胞更容易受到 lysosomal损伤和细胞死亡.
科学领域:
- 细胞生物学 细胞生物学
- 膜生物学 膜生物学
- 器官的恒常化 器官的恒常化
背景情况:
- 溶解体容易受到来自透转移,毒素和光质内容的膜损伤.
- 这种损伤可能导致溶酶体破裂和随后的细胞死亡.
- 感知和响应 lysosomal 膜张力的细胞机制至关重要.
研究的目的:
- 为了研究溶解体如何感知和响应膜张力急剧增加.
- 为了确定参与溶酶体机械感应的分子参与者.
- 了解TMEM63A在溶酶体膜完整性中的作用.
主要方法:
- 研究了TMEM63A在应对机械张力时的功能.
- 使用的细胞模型具有删除或变体TMEM63A.
- 评估了在膜张力增加的情况下对溶解的溶酶敏感性.
主要成果:
- TMEM63A 作为一个张力通道,从溶酶体中释放单价子.
- 这种阴离子流量降低了水静压和 lysosomal 膜张力.
- 缺乏功能性TMEM63A的溶解酶显著更容易发生溶解.
结论:
- 溶解体具有通过TMEM63A调节水静压和体积的机制,以应对高膜张力.
- TMEM63A在机械应力下维持 lysosomal 完整性中起着至关重要的作用.
- TMEM63A的功能障碍损害了 lysosomal 稳定性和细胞存活.
相关概念视频
Lysosomal Hydrolases
4.7K
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,...
4.7K
Lysosomes
26.9K
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,...
26.9K
Export of Misfolded Proteins out of the ER
5.4K
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...
5.4K
Delivery Pathways to the Lysosome
10.4K
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...
10.4K
Tail-anchoring of Proteins in the ER Membrane
4.0K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
4.0K
Assembly of the Lipid Bilayer in the ER
4.4K
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...
4.4K


