神经损伤诱导的蛋白2保留了 lysosomal 膜的完整性,以抑制铁亡
bioRxiv : the preprint server for biology
|February 23, 2026
概括
神经损伤诱导的蛋白2 (NINJ2) 保持了溶酶体的完整性,防止铁泄漏和铁亡. 丧失NINJ2使细胞对铁亡产生敏感性,从而提供了潜在的癌症治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 神经损伤诱导蛋白1 (NINJ1) 介导炎症细胞死亡.
- 作为NINJ1的亲属,NINJ2不会通过血破裂促进炎症.
- 在细胞过程中NINJ2的具体作用仍然不清楚.
研究的目的:
- 为了研究NINJ2在细胞平衡中的功能.
- 确定NINJ2在溶酶体膜完整性和铁亡中的作用.
- 探索NINJ2作为铁相关癌症治疗点的潜力.
主要方法:
- 免疫光检测以确定NINJ2的定位.
- 同免疫沉以确定NINJ2相互作用蛋白.
- 溶酶体膜透性试验.
- 测量细胞性铁和费里的表达.
- 在NINJ2操纵时对铁亡敏感性的分析.
- 基因沉默 (敲击) 实验. 基因沉默 (敲击) 的实验.
主要成果:
- NINJ2定位在溶解体上,并与LAMP1.1相互作用.
- 丧失NINJ2会导致溶酶体膜透和细胞体铁泄漏.
- 缺少NINJ2会增加可变铁,降低费里的表达,并促进费里的降解.
- 缺少NINJ2的细胞对诱导铁亡的药物的敏感性增加.
- 在LAMP1中断时,NINJ2倒置会逆转费里的降解.
结论:
- NINJ2对于保持 lysosomal 膜完整性和预防铁亡至关重要.
- NINJ2通过影响费里稳定性来调节细胞铁稳定.
- 对NINJ2的失调有助于铁亡,可能与慢性炎症有关.
- 在铁成癌症中,NINJ2和费里丁过度表达表明NINJ2是潜在的治疗点.
相关概念视频
Necrosis
6.8K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
6.8K
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
Regulation of the Unfolded Protein Response
3.1K
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...
3.1K
The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
Regulation of Nuclear Protein Sorting
3.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.4K
Export of Misfolded Proteins out of the ER
5.3K
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...
5.3K

