A mitochondrial oscillator dependent on reactive oxygen species

A mitochondrial oscillator dependent on reactive oxygen species

Model Status

This CellML model has been checked in both OpenCell and COR and the units are consistent. Unfortunately the model will not integrate at the moment. We are working with the model author to complete the curation of this model.

Model Structure

ABSTRACT: We describe a unique mitochondrial oscillator that depends on oxidative phosphorylation, reactive oxygen species (ROS), and mitochondrial inner membrane ion channels. Cell-wide synchronized oscillations in mitochondrial membrane potential (Delta Psi(m)), NADH, and ROS production have been recently described in isolated cardiomyocytes, and we have hypothesized that the balance between superoxide anion efflux through inner membrane anion channels and the intracellular ROS scavenging capacity play a key role in the oscillatory mechanism. Here, we formally test the hypothesis using a computational model of mitochondrial energetics and Ca(2+) handling including mitochondrial ROS production, cytoplasmic ROS scavenging, and ROS activation of inner membrane anion flux. The mathematical model reproduces the period and phase of the observed oscillations in Delta Psi(m), NADH, and ROS. Moreover, we experimentally verify model predictions that the period of the oscillator can be modulated by altering the concentration of ROS scavengers or the rate of oxidative phosphorylation, and that the redox state of the glutathione pool oscillates. In addition to its role in cellular dysfunction during metabolic stress, the period of the oscillator can be shown to span a wide range, from milliseconds to hours, suggesting that it may also be a mechanism for physiological timekeeping and/or redox signaling.

The original paper reference is cited below:

A Mitochondrial Oscillator Dependent on Reactive Oxygen Species, Sonia Cortassa, Miguel A. Aon, Raimond L. Winslow, and Brian O'Rourke, 2004, Biophysical Journal, 87, 2060-2073.PubMed ID: 15345581

Figure 1. A schematic diagram of mitochondrial energetics coupled to ROS production, transport, and scavenging. These processes are described by the equations in Cortassa et al.'s 2004 mathematical model
Figure 2. A schematic diagram of the reactions used in the model of the glycogenolysis pathway in skeletal muscle.