Cortassa, Aon, Winslow, O'Rourke, 2004

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

In order to be able to rapidly adapt to environmental changes, biological systems require dynamic control systems which function near the edge of instability. Dynamic control can be in the form of oscillations, such as cytosolic calcium concentration oscillations(eg Sneyd et al., Modelling the Control of Calcium Oscillations by Membrane Fluxes, 2004), electrical pacemaker cells (eg Lovell et al., A Gradient Model Of Cardiac Pacemaker Myocytes, 2004), and secretion of insulin from pancreatic islets (eg Keener, A Model of Diffusion Induced Oscillatory Insulin Secretion in Pancreatic Beta Cells, 2001)

Oscillations in energy metabolism also occur for example in mitochondria, there are oscillations in the transmembrane ionic currents. Experimental data have shown that oscillation of the mitochondrial energy state occur as a consequence of the interactions between mitochondrial reactive oxygen species (ROS) production and the ROS scavenging systems of the cell. In the current study, Cortassa et al. use this experimental data as the basis for their mathematical model, which incorporates mitochondrial ROS synthesis, ROS scavenging, and ion channels within the mitochondrial membrane (see Figure 1 below). This mathematical model of a mitochondrial oscillator is embedded within a previously published model of cardiac mitochondrial energetics (see Cortassa et al. Modelling Mitochondrial Energy Metabolism, 2003, and also see Figure 2 below for more details)

Model simulations have generated data which match experimental results. Furthermore, the model simulations also demonstrate that the period of the mitochondrial oscillator can be modulated over a wide range of timescales, from milliseconds to hours, by altering a single parameter, the rate of ROS scavenging by the enzyme superoxide dismutase.

The complete 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. (Full text (HTML) and PDF versions of the article are available to subscribers on the Biophysical Journal website.) 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.