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A mitochondrial oscillator dependent on reactive oxygen species
Sonia Cortassa1, Miguel A Aon, Raimond L Winslow
1The Johns Hopkins University, Institute of Molecular Cardiobiology and Center for Cardiovascular Bioinformatics and Modeling, Baltimore, Maryland 21205-2195, USA.
Biophysical Journal
|September 4, 2004
Summary
A novel mitochondrial oscillator, driven by oxidative phosphorylation and reactive oxygen species (ROS), synchronizes cell-wide functions. This mechanism, involving ion channels, may regulate physiological timing and redox signaling.
Area of Science:
- Mitochondrial physiology
- Cellular energetics
- Redox biology
Background:
- Synchronized oscillations in mitochondrial membrane potential (Delta Psi(m)), NADH, and ROS have been observed in cardiomyocytes.
- The interplay between superoxide anion efflux and ROS scavenging capacity is hypothesized to be crucial for this oscillatory mechanism.
Purpose of the Study:
- To computationally model and experimentally validate a mitochondrial oscillator mechanism.
- To investigate the roles of oxidative phosphorylation, reactive oxygen species (ROS), and inner membrane ion channels in mitochondrial oscillations.
Main Methods:
- Development of a computational model integrating mitochondrial energetics, Ca(2+) handling, ROS production/scavenging, and inner membrane ion flux.
- Experimental validation of model predictions regarding oscillator period modulation and glutathione redox state oscillations.
Main Results:
- The computational model accurately reproduced observed oscillations in Delta Psi(m), NADH, and ROS.
- Experimental results confirmed that ROS scavenger concentration and oxidative phosphorylation rate modulate the oscillator's period.
- Oscillations in the glutathione redox state were experimentally verified.
Conclusions:
- The study describes a unique mitochondrial oscillator dependent on oxidative phosphorylation, ROS, and ion channels.
- The oscillator's period is tunable, suggesting potential roles in physiological timekeeping and redox signaling beyond cellular dysfunction.