辅助子单元NDUFB4参与线粒体复合体I超复合体的形成.
Gaganvir Parmar1, Claire Fong-McMaster1, Chantal A Pileggi1
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ontario, Canada.
The Journal of biological chemistry
|January 11, 2024
概括
线粒体呼吸超级复合体 (SCs) 对于细胞能量至关重要. NDUFB4突变破坏了呼吸体组合,损害了线粒体功能和新陈代谢,突出了SCs.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 呼吸系统超级复合体 (SCs) 是线粒体电子运输链复合体的超分子组合.
- 在线粒体呼吸功能中SCs的确切作用及其组装机制,特别是I1III2IV1呼吸体,尚未完全理解.
- 在SC的功能障碍与神经退行症和代谢综合征有关.
研究的目的:
- 研究NDUFB4子单元在呼吸超复合体的组装和功能中的作用.
- 使用特定的NDUFB4点突变,破译细胞代谢中含有I1III2的呼吸道SCs的功能.
- 在研究SCs时,尽量减少对复杂I组件的功能后果.
主要方法:
- 在NDUFB4子单元中引入特定的点突变 (N24A和R30A).
- 呼吸体组合和线粒体呼吸流量的分析.
- 稳定状态代谢学,以评估细胞代谢物的变化.
主要成果:
- NDUFB4点突变N24A和R30A显著损害了I1III2IV1呼吸酶组.
- 突变导致线粒体呼吸流量减少.
- 代谢学揭示了酸循环代谢物的全球减少,影响NADH生成基质.
结论:
- NDUFB4在I1III2IV1呼吸体组装中发挥着不可或缺的作用.
- 呼吸系统超级复合体在调节哺乳动物细胞生物能量方面具有功能意义.
- 破坏SCs影响细胞代谢,对代谢疾病有影响.
相关概念视频
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
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
ATP Synthase: Mechanism
14.6K
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...
14.6K
Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K
Mitochondrial Protein Sorting
4.3K
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...
4.3K


