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Updated: Jun 24, 2026
12:22
Ratiometric Biosensors that Measure Mitochondrial Redox State and ATP in Living Yeast Cells
Published on: July 22, 2013
Degenerative diseases, oxidative stress and cytochrome c oxidase function
Bernhard Kadenbach1, Rabia Ramzan, Sebastian Vogt
1Fachbereich Chemie, Philipps-University, D-35032 Marburg, Germany. Kadenbach@staff.uni-marburg.de
Trends in Molecular Medicine
|March 24, 2009
Summary
High ATP levels normally inhibit cellular respiration via cytochrome c oxidase (CcO), preventing excess reactive oxygen species (ROS) and mitochondrial damage. Stress disrupts this, increasing ROS and potentially driving degenerative diseases.
Area of Science:
- Biochemistry
- Cellular Biology
- Mitochondrial Function
Background:
- Aging and degenerative diseases correlate with elevated reactive oxygen species (ROS).
- Mitochondrial membrane potential influences ROS production.
- Existing models link high membrane potential to increased ROS.
Purpose of the Study:
- To investigate a novel, membrane potential-independent mechanism of cellular respiratory control.
- To elucidate the role of allosteric inhibition of cytochrome c oxidase (CcO) by ATP.
- To establish a molecular link between cellular stress and degenerative diseases via ROS regulation.
Main Methods:
- Studied allosteric inhibition of cytochrome c oxidase (CcO) by ATP:ADP ratios.
- Investigated the effect of cellular stress on CcO dephosphorylation.
- Monitored changes in mitochondrial membrane potential and ROS production.
Main Results:
- Identified a second respiratory control mechanism: allosteric inhibition of CcO by high ATP:ADP ratios, independent of membrane potential.
- Demonstrated that stress-induced dephosphorylation of CcO abolishes ATP inhibition.
- Observed increased mitochondrial membrane potential and ROS levels upon stress-induced CcO dephosphorylation.
Conclusions:
- Feedback inhibition of CcO by ATP maintains low membrane potential and ROS levels.
- Stress-induced dephosphorylation of CcO activates respiration, increasing ROS and potentially contributing to degenerative diseases.
- This mechanism provides a molecular link between stress and age-related diseases.
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