压力诱导的微自与溶酶体生物发生协调,并由PIKfyve调节
Alison D Klein1,2, Kayla L Petruzzi2, Chan Lee1,2
1BCMB Graduate Program, Weill Cornell Medical College, New York, NY 10065.
Molecular biology of the cell
|March 27, 2024
概括
细胞压力通过微自,由PIKfyve调节的过程触发了溶酶体的周转. 这种途径与溶酶体生物生成不同,涉及特定的蛋白质LC3循环和内囊泡的形成.
科学领域:
- 细胞生物学 细胞生物学
- 自学研究 自学研究
- 溶酶体生物学 溶酶体生物学
背景情况:
- 溶酶体的周转和生物发生是已知的对破坏膜的药物的反应.
- 在其他压力条件下溶酶体平衡的机制尚不清楚.
- 选择性溶解体循环通过微自以前与代谢压力和特定的化学处理有关.
研究的目的:
- 为了研究脂类激酶PIKfyve在溶酶体微自的作用.
- 阐明PIKfyve活动,TFEB核转位和溶酶体生物发生之间的关系.
- 在压力下区分 lysosome 生物发生和微自的调节途径.
主要方法:
- 用诱导 lysosomal 压力的药物进行细胞治疗.
- 分析微自诱导和LC3脂化.
- 调查PIKfyve活动和TFEB核转移.
- 使用自缺陷细胞和基因依赖性测试.
主要成果:
- 确定了一种依赖于PIKfyve活动的微自诱导的新型形式.
- 在微自过程中,PIKfyve对于内囊泡的形成和LC3周转是必不可少的.
- TFEB激活是溶酶体生物发生的媒介,需要非正规的自,但不是PIKfyve.
- 在调节微自方面,PIKfyve作用于非正规自的下游.
结论:
- 在特定的压力条件下, lysosome 微自受 PIKfyve 调节,这是非正规自的下游.
- PIKfyve对于内囊泡的形成和LC3的周转至关重要,这是这个微自途径中的关键事件.
- 通过TFEB激活来调节 lysosome生物发生,与PIKfyve依赖的微自法不同.
相关概念视频
01:36Delivery Pathways to the Lysosome
6.5K
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...
6.5K
01:27Autophagy
4.2K
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,...
4.2K
01:18Autophagic Cell Death
3.4K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.4K
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
01:31Regulation of the Unfolded Protein Response
2.4K
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...
2.4K
02:58Regulated Protein Degradation
7.2K
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...
7.2K