哈达 (HADHA) 调节呼吸系统复杂的组装和配对 粮农组织和OXPHOSOS
Chaoying Qin1,2, Shasha Gong1,3, Ting Liang1
1Department of Cell Systems and Anatomy, The University of Texas Health San Antonio, San Antonio, Texas, 78229, USA.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|November 3, 2024
概括
线粒体三功能蛋白子单元α (HADHA) 调节超级复合体 (SC) 的组合,并将脂肪酸氧化 (FAO) 与氧化酸化 (OXPHOS) 结合起来. 缺少HADHA会损害这两种能量通路,突出显示它在细胞生物能量学中的关键作用.
科学领域:
- 线粒体的生物能量学
- 细胞代谢的细胞代谢.
- 蛋白质组学是指蛋白质组学.
背景情况:
- 氧化酸化 (OXPHOS) 和脂肪酸氧化 (FAO) 是定位在线粒体中的关键能量通路.
- 在患者中观察到OXPHOS和FAO的二次缺陷,但机制尚不清楚.
- 线粒体超级复合体 (SCs) 的组合与脂质代谢有关.
研究的目的:
- 为了研究线粒体三功能蛋白 (MTP) 子单元α (HADHA) 在SCs组装中的作用.
- 阐明粮农组织与OXPHOS之间的合机制.
主要方法:
- 蛋白质组学分析以确定调节因素.
- 哈达敲除细胞和敲除小鼠胚胎纤维细胞 (MEFs).
- 在小鼠中用银河糖和高脂肪饮食 (HFD) 培养细胞.
主要成果:
- 蛋白质组学将HADHA确定为SCs组装的潜在调节者.
- 缺少HADHA导致SCs组装减少和OXPHOS有缺陷.
- 刺激OXPHOS或脂质代谢增加了HADHA的表达.
- 被HFD养的HADHA异质合体小鼠显示出肥胖症,SCs组合减少,OXPHOS受损.
结论:
- 哈达是线粒体超级复杂组合的关键因素.
- 哈达结合了脂肪酸氧化和氧化酸化.
- 哈达在维持细胞能量平衡中起着至关重要的作用.
相关概念视频
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
7.1K
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...
7.1K
Respiration Pathways
1
Cellular respiration is a fundamental metabolic process that enables organisms to generate energy from organic molecules. One of its central pathways is the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, which plays a crucial role in energy production and biosynthetic processes.Conversion of Pyruvate to Acetyl-CoAThe pyruvate generated from glycolysis undergoes oxidative decarboxylation by the pyruvate dehydrogenase complex, producing acetyl-CoA, one molecule of NADH, and one...
1
Electron Transport Chain: Complex I and II
11.9K
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...
11.9K
The Electron Transport Chain
16.2K
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...
16.2K
Pyruvate Oxidation
158.5K
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
158.5K


