由MTCH2和F-ATP合成酶介导的线粒体透性过渡有助于铁亡防御
1Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
FEBS letters
|September 3, 2024
概括
线粒体载体同位素2 (MTCH2) 连接线粒体透性过渡孔 (PTP) 和外膜透性 (MOMP). 这种相互作用调节铁亡防御,突出了PTP在细胞死亡途径中的新角色.
科学领域:
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
- 生物化学 生物化学
背景情况:
- 线粒体透性过渡孔 (PTP) 开放导致线粒体外膜透性 (MOMP) 和细胞死亡,但该机制尚未完全理解.
- 已知线粒体载体同源2 (MTCH2) 通过招募tBID来调解MOMP.
- 环素D (CyPD) 是PTP开放的一个关键调节剂.
研究的目的:
- 阐明PTP打开诱导MOMP的机制.
- 调查MTCH2在协调PTP和MOMP中的作用.
- 为了确定线粒体透性过渡在铁亡中的参与.
主要方法:
- 同免疫沉试验用于研究蛋白质相互作用.
- 细胞活力测试用于评估ferroptosis.
- 基因淘汰实验 (CyPD,MTCH2,子单位j).
主要成果:
- MTCH2与CyPD结合,并通过子单元j促进F-ATP合成酶二元化.
- 复杂的MTCH2-CyPD子单位协调PTP和MOMP.
- 击败CyPD,MTCH2或子单位j使细胞对ferroptosis敏感,而ferroptosis则被MitoTEMPO抑制.
结论:
- MTCH2,CyPD和F-ATP合成酶子单元形成一个连接PTP和MOMP的复合体.
- 线粒体透性过渡是铁亡防御的关键调解者.
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
902
08:21F1FO ATPase Vesicle Preparation and Technique for Performing Patch Clamp Recordings of Submitochondrial Vesicle Membranes
Published on: May 4, 2013
10.2K
相关概念视频
ATP Synthase: Mechanism
14.2K
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...
14.2K
Translocation of Proteins into the Mitochondria
3.1K
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,...
3.1K
Energy to Drive Translocation
2.0K
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...
2.0K
Electron Transport Chain: Complex I and II
12.3K
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...
12.3K
Mitochondrial Membranes
9.3K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
9.3K
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
