Modelling the redox imbalance in Dominant Optic Atrophy: the case of respiratory Complex I

Abstract

Dominant Optic Atrophy is a neuro-ophthalmic disease characterized by the degeneration of the optic nerves. As other neurodegenerative diseases, this pathology was associated with dysfunctional mitochondrial respiratory complexes and an increased production of Reactive Oxygen Species (ROS). Our objective is to create a mathematical model of the molecular mechanisms involved in the pathogenesis of Dominant Optic Atrophy in order to predict their evolution and give appropriated treatment based on in-silico analysis with physiological parameters from a specific patient. The first part of the work presented here concerns processes and feedback mechanisms of the whole dysfunctional mitochondrial system. The behaviour of the system is explained with a block diagram. In the second part, we present a detailed stochastic model of catalytic activity and ROS production of respiratory complex I. We developed the model using a Petri net formalism and a continuous-time Markov chains theory. The simulations were realized on Matlab and compared to kinetic data from the literature. Our model is able to reproduce the dynamics of the complex I system and to simulate observed behaviours of this system regarding ROS production.