Related Experiment Video

Updated: Sep 29, 2025

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
08:57

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

Published on: February 24, 2018

10.2K

Cytochrome c Oxidase Inhibition by ATP Decreases Mitochondrial ROS Production

Rabia Ramzan1, Amalia M Dolga2, Susanne Michels3

  • 1Mitochondrial Bioenergetics' Lab, Department of Heart Surgery, University Hospital of Giessen and Marburg (UKGM), Baldingerstrasse 1, D-35043 Marburg, Germany.

Cells
|March 25, 2022
PubMed

Insights

High ATP levels inhibit cytochrome c oxidase (CytOx) in heart mitochondria, decreasing reactive oxygen species (ROS) production. This ATP-induced inhibition leads to static mitochondrial respiration and membrane potential.

Area of Science:

  • Mitochondrial physiology
  • Biochemistry
  • Cellular respiration

Background:

  • Cytochrome c oxidase (CytOx) is a key enzyme in mitochondrial electron transport.
  • Allosteric ATP inhibition of CytOx is a critical regulator of mitochondrial function.
  • Maintaining a high ATP/ADP ratio is essential for studying CytOx activity and mitochondrial respiration.

Purpose of the Study:

  • To investigate the consequences of CytOx inhibition by ATP at high ATP/ADP ratios in isolated rat heart mitochondria.
  • To determine the effect of ATP-induced CytOx inhibition on mitochondrial respiration, membrane potential (ΔΨm), and reactive oxygen species (ROS) production.

Main Methods:

  • Isolated rat heart mitochondria were used.
  • CytOx activity was measured under conditions of high ATP/ADP ratio.
  • Mitochondrial respiration, membrane potential (ΔΨm), and ROS production were monitored.
  • Inhibition of the electron transport chain by antimycin A was used as a control.

Main Results:

  • ATP inhibition of CytOx resulted in static mitochondrial respiration and membrane potential (ΔΨm).
  • ROS production was markedly decreased when CytOx was inhibited by ATP.
  • Similar results were observed when the electron transport chain was inhibited by antimycin A, leaving only CytOx functional.

Conclusions:

  • ATP binding to CytOx is the primary cause of decreased mitochondrial ROS production.
  • ATP-induced CytOx inhibition leads to static mitochondrial respiration and membrane potential.
  • This study highlights the regulatory role of ATP in modulating mitochondrial energy production and ROS generation.
Keywords:
ATPROScytochrome c oxidasemitochondrial membrane potential

More Related Videos

Isolation of Mitochondria from Mouse Skeletal Muscle for Respirometric Assays08:11

Isolation of Mitochondria from Mouse Skeletal Muscle for Respirometric Assays

Published on: February 10, 2022

5.3K
Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

2.6K

Related Concept Videos

The Electron Transport Chain01:30

The Electron Transport Chain

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...
17.6K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

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...
15.2K
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

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...
15.4K
Electron Transport Chain: Complex III and IV01:43

Electron Transport Chain: Complex III and IV

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...
8.2K
Chemiosmosis and ATP Synthesis01:22

Chemiosmosis and ATP Synthesis

The electron transport chain is a critical component of cellular respiration, occurring in the inner mitochondrial membrane. It facilitates the transfer of high-energy electrons from reduced cofactors NADH and FADH₂ to molecular oxygen, the final electron acceptor. This transfer of electrons through a series of protein complexes is tightly coupled to the translocation of protons across the membrane, generating a proton gradient essential for ATP synthesis.Electron Flow and Proton...
327
Chemiosmosis01:32

Chemiosmosis

Oxidative phosphorylation is a highly efficient process that generates large amounts of adenosine triphosphate (ATP), the basic unit of energy that drives many cellular processes. Oxidative phosphorylation involves two processes— the electron transport chain and chemiosmosis.
Electron Transport Chain
The electron transport chain involves a series of protein complexes on the inner mitochondrial membrane that undergo a series of redox reactions. At the end of this chain, the electrons...
103.6K