Phenomenological equations for electron transport chain-mediated reactive oxygen species metabolism

Reactive oxygen species (ROS) are produced as metabolic by-products throughout the cell, including within the mitochondria by, among others, the electron transport chain (ETC). ROS are important signalling molecules, but their accumulation can lead to oxidative stress. As experimental protocols to measure cellular ROS levels can suffer from limitations, computational models can complement experimental measurements to elucidate mechanisms underlying ROS metabolism. Phenomenological models utilise reduced equation sets to relate aspects of ROS metabolism to measured bioenergetic parameters such as the mitochondrial membrane potential or NADH concentration, and often generate experimentally testable hypotheses. Integrating multiple bioenergetic parameters, we here describe a phenomenological equation-based model of ETC-mediated ROS metabolism implemented by expanding an existing thermodynamic model of the ETC. We demonstrate that this model can reproduce experimentally observed behaviour, and explore how the model can be applied to gain insight into ROS metabolism in the presence of pathology. Model predictions suggest that failure of scavenging may be more harmful to cells than respiratory complex impairment.