在ER-线粒体接触点的PDZD8-FKBP8连接复合物调节线粒体复杂性
bioRxiv : the preprint server for biology
|June 19, 2024
概括
研究人员确定FKBP8是外线粒体膜 (OMM) 蛋白质,与ER蛋白PDZD8结合,形成关键的线粒体-ER膜接触点 (MERCS) 并调节线粒体形态.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体-ER膜接触点 (MERCS) 对细胞生化和生理学至关重要.
- ER蛋白PDZD8对于MERCS形成至关重要,但其线粒体结合伙伴是未知的.
研究的目的:
- 为了识别与PDZD8.8相互作用的外部线粒体膜 (OMM) 蛋白质.
- 阐明这种相互作用在MERCS形成和线粒体形态学中的作用.
主要方法:
- 没有偏见的近距离蛋白质组学
- 在CRISPR-Cas9内源性蛋白质标记上.
- 低温电子显微镜 (Cryo-EM) 断层扫描
- 相对应的光-EM (CLEM) 的
- 单个分子跟踪跟踪.
主要成果:
- FKBP8被确定为PDZD8.8的OMM连接合作伙伴.
- PDZD8在ER膜上表现出动态扩散,停留在MERCS.
- FKBP8调节ER-OMM距离;这两种蛋白质对于MERCS形成是相互依赖的.
- PDZD8以FKBP8依赖的方式增强了线粒体的复杂性.
结论:
- 一种涉及PDZD8和FKBP8的新型ER-线粒体结合复合体已被确定.
- 这种复合体在调节哺乳动物细胞中的线粒体形态学方面发挥着关键作用.
更多相关视频
08:27Visualization and Quantification of Endogenous Intra-Organelle Protein Interactions at ER-Mitochondria Contact Sites by Proximity Ligation Assays
Published on: October 20, 2023
1.6K
08:37Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
Published on: June 1, 2017
14.1K
相关概念视频
The Supercomplexes in the Crista Membrane
2.5K
The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
2.5K
The Inner Mitochondrial Membrane
3.3K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.3K
Electron Transport Chain: Complex I and II
12.9K
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...
12.9K
The ADP/ATP Carrier Protein
3.2K
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
3.2K
Energy to Drive Translocation
2.1K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.1K
Electron Transport Chains
98.0K
The final stage of cellular respiration is oxidative phosphorylation that consists of two steps: the electron transport chain and chemiosmosis. The electron transport chain is a set of proteins found in the inner mitochondrial membrane in eukaryotic cells. Its primary function is to establish a proton gradient that can be used during chemiosmosis to produce ATP and generate electron carriers, such as NAD+ and FAD, that are used in glycolysis and the citric acid cycle.
The ETC is comprised of...
The ETC is comprised of...
98.0K
