防止线粒体逆电子运输作为心脏保护策略
Hiran A Prag1, Michael P Murphy2,3, Thomas Krieg4
1Department of Medicine, University of Cambridge, Cambridge, CB2 0QQ, UK. hap38@cam.ac.uk.
Basic research in cardiology
|August 28, 2023
概括
通过线粒体复合体I的逆电子运输产生超氧化物,在心肌梗塞后的再输液过程中引发心脏损伤. 针对这个过程可能会提供心脏保护,防止缺血症/再输液损伤.
科学领域:
- 线粒体的生物化学
- 心血管病理生理学
- 缺血症/再输液损伤 缺血症/再输液损伤
背景情况:
- 心肌梗塞导致缺血/再输血 (I/R) 损伤.
- 线粒体复合体I在I/R过程中通过反向电子运输 (RET) 产生超氧化物.
- 这种超氧化物爆发是细胞损伤的关键驱动因素.
研究的目的:
- 阐明使RET在复合体I产生超氧化物的条件.
- 为了解释在再输血阶段出现RET的情况.
- 确定针对RET进行心脏保护的治疗策略.
主要方法:
- 审查关于线粒体功能和I/R损伤的现有文献.
- 分析有助于RET的途径.
- 探索潜在的治疗干预措施.
主要成果:
- 定义了RET介导的超氧化物生成在复合体I所需的特定条件.
- 描述了反和RET之间的机制联系.
- 确定了在I/R条件下促进RET的关键途径.
结论:
- 线粒体复合体I中的RET是I/R诱导的心肌损伤的关键因素.
- 了解RET机制为心脏保护疗法提供了目标.
- 旨在抑制RET的干预措施显示出治疗心肌梗塞的前景.
相关概念视频
Electron Transport Chain: Complex I and II
14.5K
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...
14.5K
The Electron Transport Chain
16.9K
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...
16.9K
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
Electron Transport Chain: Complex III and IV
7.6K
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...
7.6K
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
Electron Transport Chains
99.3K
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...
99.3K


