通过超硫化物介导的线粒体呼吸和调节蛋白质质量的长寿控制
Akira Nishimura1, Sunghyeon Yoon2, Tetsuro Matsunaga2
1Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.
Redox biology
|January 10, 2024
概括
这项研究表明,由cysteinyl-tRNA合成酶 (CARS) 生产的超硫化物对于线粒体功能和酵母的寿命至关重要. 补充超硫化物延长了寿命,突出了它们的生物学意义.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 细胞衰老 细胞衰老
背景情况:
- 超硫化物,是带有连接硫原子的硫种,在生物研究中越来越受到关注.
- 最近通过cysteinyl-tRNA合成酶 (CARS) 确定了囊硫酸盐 (CysSSH) 和相关的超硫酸盐的依赖于酸盐 (PLP) 的生物合成.
研究的目的:
- 调查囊硫化物 (CysSSH) 在芽酵母 (Saccharomyces cerevisiae) 中的生理作用.
- 阐明CARS,超硫化物代谢,线粒体功能和时间老化之间的联系.
主要方法:
- 在酵母CRS1 (CARS ortholog) 中产生了PLP结合部位突变 (K109A),以损害超硫化物合成.
- 评估了突变酵母菌的时间性衰老,内质网膜压力和线粒体生物能学.
- 使用外源超硫化物捐赠者来测试救援效应.
主要成果:
- 在CARS中的K109A突变减少了CysSSH和超硫化物合成.
- 突变酵母表现出时间衰老的减少,细胞内膜网膜压力的增加和线粒体生物能学的损害.
- 外源的超硫化物捐赠者拯救了减少的时间衰老表型.
结论:
- 氨基-tRNA合成酶 (CARS) 在超硫化物的产生和代谢中发挥着关键作用.
- 超硫化物对于维护线粒体功能和调节酵母的寿命至关重要.
- 通过CARS介导的超硫化物代谢是细胞衰老和应激反应的关键因素.
相关概念视频
Mitochondria
12.7K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
12.7K
Electron Transport Chain: Complex III and IV
7.5K
During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
7.5K
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
Regulated Protein Degradation
7.3K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.3K
Electron Transport Chain: Complex I and II
13.4K
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...
13.4K
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


