反应性氧物种控制线粒体进口门中的蛋白质降解
Rachael McMinimy1, Andrew G Manford2, Christine L Gee3
1Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
Molecular cell
|December 6, 2024
概括
低反应性氧物种 (ROS) 水平引发了减少性应激反应. 这种反应由库林2-FEM1同源B (CUL2FEM1B) 中介,维持线粒体功能和细胞存活.
科学领域:
- 线粒体生物学 线粒体生物学
- 细胞应激反应细胞应激反应
- 生物化学 生物化学
背景情况:
- 反应性氧物种 (ROS) 与衰老和神经退行有关.
- 持续耗尽基底ROS会破坏细胞功能.
- 减少应激反应对抗ROS损失,但其ROS传感器是未知的.
研究的目的:
- 确定通过减轻应激反应途径感知到的ROS.
- 阐明减少性压力影响线粒体功能的机制.
- 确定基底ROS在细胞适应和生存中的作用.
主要方法:
- 生物化学测试以确定酶活性.
- 线粒体复合体分析.
- 基质降解研究.
主要成果:
- 库林2-FEM1同源B (CUL2FEM1B) 作为减轻应激反应中的中心酶.
- CUL2FEM1B针对线粒体TOM复合体,从电子运输链 (ETC) 复合体III中感知ROS.
- 消耗ROS导致CUL2FEM1B基质降解,支持线粒体进口和ETC复合体IV生物发生.
结论:
- 基底ROS作为线粒体活动的哨兵.
- 细胞通过ROS信号调整ETC功能,以响应环境线索.
- 这种机制对于细胞分化和生存至关重要.
相关概念视频
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
Electron Transport Chain: Complex III and IV
7.0K
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...
7.0K
The Electron Transport Chain
16.1K
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...
16.1K
Mitochondrial Precursor Proteins
2.5K
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
Most of the mitochondrial...
2.5K
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
Mitochondrial Membranes
8.6K
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,...
8.6K


