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相关概念视频

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

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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...
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Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

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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...
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Electron Transport Chain: Complex III and IV01:43

Electron Transport Chain: Complex III and IV

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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...
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Structure of Porins01:21

Structure of Porins

3.8K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
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Mitochondrial Membranes01:45

Mitochondrial Membranes

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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,...
16.5K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

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Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
4.5K

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相关实验视频

Updated: Jan 7, 2026

Inner Mitochondrial Membrane Sensitivity to Na+ Reveals Partially Segmented Functional CoQ Pools
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利用共识对人类线粒体综合体I和III的对接方法.

Karin Grillberger1, Viktoria Magel2, Marcel Leist2

  • 1Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna 1090, Austria.

Chemical research in toxicology
|December 30, 2025
PubMed
概括

基于结构的分子对接通过排名化合物危险来有效预测毒性. 这种方法,特别是共识评分,解决了传统QSAR错过的活动悬崖等挑战,有助于优先考虑更安全的化学化合物.

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Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
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Author Spotlight: Unveiling Oxidative Phosphorylation System Dynamics and Mitochondrial Roles in Health and Disease
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相关实验视频

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Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
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科学领域:

  • 计算化学的计算化学
  • 毒理学 毒理学 毒理学
  • 药物发现 药物发现 药物发现

背景情况:

  • 像分子对接这样的基于结构的方法在毒性预测中未得到充分利用.
  • 传统的定量结构 - 活动关系 (QSAR) 方法面临着挑战,例如由立体异构引起的活动悬崖.

研究的目的:

  • 评估分子对接评分功能和相互作用指纹,以预测针对人类线粒体复合体I和III (CI,CIII) 的化合物的毒性.
  • 评估这些基于结构的方法在识别活动悬崖和优先考虑安全的化合物的实用性.

主要方法:

  • 诱导适合对接协议以建模结合点灵活性.
  • 应用各种对接评分功能和蛋白质 - 配体相互作用指纹.
  • 尽量减少用于重刻的绑定能量.
  • 与实验数据和体外试验相关的等级相关性分析.

主要成果:

  • 个人和共识对接得分都显示了可接受的等级相关性与CIII的实验数据.
  • 共识相互作用指纹在CIII.III区分抑制剂亚型.
  • 在体外试验证实了在CI上对E-/Z-Fenpyroximate的异构依赖性活性悬崖.

结论:

  • 共识对接和评分作为有价值的选工具,以根据预测的结合亲和关系来优先考虑化合物.
  • 这些基于结构的方法增强了毒性预测,特别是对于复杂的情况,如立体异构驱动的活动悬崖.