调节线粒体透性过渡孔开放通过单价在肝脏线粒体中的单价
Ekaterina S Kharechkina1, Anna B Nikiforova1, Alexey G Kruglov1
1Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, Pushchino, 142290 Moscow, Russia.
International journal of molecular sciences
|June 10, 2023
概括
单价酸,包括 (K+),刺激线粒体透性过渡孔 (PTP) 开放,这是细胞死亡的关键事件. 这种阴子诱导的PTP开放涉及抑制的K+/H+交换和矩阵酸化.
科学领域:
- 线粒体生理学线粒体生理学
- 细胞死亡途径的细胞死亡途径.
- 离子运输 离子运输
背景情况:
- 线粒体透性过渡孔 (PTP) 开放对于细胞死亡在病理状况如缺血/再输液等过程中至关重要.
- (K+) 运输到线粒体中可以防止缺血/反损伤.
- 在规范PTP开放方面,K+运输的确切作用仍然不完全理解.
研究的目的:
- 研究 (K+) 和其他单价在调节PTP开放中的作用.
- 阐明在体外模型中子影响PTP开放的机制.
主要方法:
- 使用标准的光谱和电极技术来监测PTP开放.
- 测量了线粒体膜潜力,Ca2+保留能力,矩阵pH和K+运输.
- 采用体外模型系统来研究子对PTP的影响.
主要成果:
- 与糖相比,所有测试的酸盐 (K +,Na +,胆 +,Li +) 都显著刺激了PTP的开放.
- 研究了潜在的机制,包括离子强度,通道/交换器活性,Ca2+/H+交换抑制和离子流入.
- 数据表明,阴离子诱导的PTP开放通过抑制K+/H+交换和矩阵酸化来调解,从而促进酸盐流入.
结论:
- 离子流入,特别是K+,在刺激PTP开放方面发挥着重要作用.
- K+/H+交换器,酸盐载体和选择性K+通道构成了PTP的调节三位一体.
- 这种PTP调节三位一体可能在体内运作,影响细胞存活和死亡.
相关概念视频
Structure of Porins
3.0K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.0K
Translocation of Proteins into the Mitochondria
3.2K
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,...
3.2K
Protein Transport into the Inner Mitochondrial Membrane
3.9K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
3.9K
Electron Transport Chain: Complex I and II
14.6K
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...
14.6K
Mitochondrial Membranes
11.6K
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,...
11.6K
Mitochondrial Protein Sorting
4.4K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K


