在Fis1中隐藏的一种囊,旨在防止氧化应激下过度的线粒体裂变和功能障碍
Suman Pokhrel1,2, Gwangbeom Heo1, Irimpan Mathews3
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
Nature communications
|May 6, 2025
概括
氧化应激会导致Fis1蛋白改变形状,暴露Cys41. 这导致线粒体分裂和功能障碍,但SP11保护细胞.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 病理学 病理学 病理学
背景情况:
- Fis1蛋白调解Drp1的线粒体局部化,导致与氧化应激相关的病理中过度的线粒体裂变.
- 通过Fis1检测氧化应激并促进DRp1招募的机制尚不清楚.
研究的目的:
- 为了阐明Fis1介导的线粒体裂变的机制,以应对氧化应激.
- 确定Fis1中的结构变化,从而触发Drp1的招聘.
- 探索针对Fis1激活的治疗潜力.
主要方法:
- 使用结构生物学研究了Fis1的形状变化.
- 利用了缺乏Cys41.1的基因工程细胞系.
- 描述了小分子SP11及其与激活Fis1的相互作用.
- 在氧化应激下用SP11治疗的细胞中评估线粒体完整性和功能.
主要成果:
- 氧化应激诱导Fis1的结构变化,暴露Cys41.
- 激活的Fis1通过Cys41形成共价同极体,增强Drp1的招募和线粒体裂变.
- 小分子SP11选择性地与Cys41.1处的激活Fis1结合.
- SP11治疗可以在经历氧化应激的细胞中保持线粒体的完整性和功能.
- 缺少Cys41的细胞系显示Fis1同质化和线粒体分裂减少.
结论:
- 通过Cys41暴露和同质化,Fis1充当氧化应激传感器,导致过度的线粒体裂变.
- SP11显示出作为Fis1介导的线粒体功能障碍特征的疾病的治疗剂的潜力.
更多相关视频
04:01Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
792
07:16Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
1.6K
相关概念视频
Electron Transport Chain: Complex I and II
9.6K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
9.6K
Translocation of Proteins into the Mitochondria
3.0K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
The Electron Transport Chain
15.8K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
15.8K
ATP Synthase: Mechanism
13.7K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
13.7K
The Proteasome
779
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...
779
