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Related Concept Videos

The Electron Transport Chain01:30

The Electron Transport Chain

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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.
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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.
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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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Related Experiment Video

Updated: Oct 17, 2025

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

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Structural Basis for Inhibition of ROS-Producing Respiratory Complex I by NADH-OH.

Marta Vranas1,2, Daniel Wohlwend1, Danye Qiu3

  • 1Institute of Biochemistry, University of Freiburg, 79104, Freiburg, Germany.

Angewandte Chemie (International Ed. in English)
|October 6, 2021
PubMed
Summary

The structure of NADH-OH, a novel inhibitor of respiratory complex I, was determined using X-ray crystallography. This reveals key interactions and provides a basis for developing new mitochondrial reactive oxygen species (ROS) suppressors.

Keywords:
NADH:ubiquinone oxidoreductaseelectron transportinhibitorsreactive oxygen speciesstructural biology

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Related Experiment Videos

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Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry
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Area of Science:

  • Biochemistry
  • Structural Biology
  • Mitochondrial Physiology

Background:

  • Respiratory Complex I (NADH:ubiquinone oxidoreductase) is crucial for cellular energy metabolism and a primary source of reactive oxygen species (ROS).
  • Mitochondrial dysfunction and ROS contribute to aging and various diseases.
  • Existing methods to elucidate the structure of the novel inhibitor NADH-OH have been unsuccessful.

Purpose of the Study:

  • To determine the molecular structure of NADH-OH bound to respiratory Complex I.
  • To identify the specific amino acid residues involved in NADH-OH binding.
  • To understand the mechanism of NADH-OH inhibition and its implications for ROS regulation.

Main Methods:

  • X-ray crystallographic analysis of a soluble fragment of Complex I with bound NADH-OH.
  • High-resolution (2.0 Å) structural determination.
  • Analysis of amino acid interactions within the active site.

Main Results:

  • The precise structure of NADH-OH within the active site of Complex I was elucidated.
  • Specific amino acid residues essential for NADH-OH binding were identified.
  • The unique binding of NADH-OH to the Complex I Rossmann-fold was revealed, suggesting a regulatory role in ROS generation.

Conclusions:

  • The determined structure provides critical insights into NADH-OH's mechanism of action.
  • NADH-OH is a potent inhibitor of Complex I-mediated ROS production.
  • NADH-OH serves as a lead compound for developing novel mitochondrial ROS suppressors.