MITODYN: An Open Source Software for Quantitative Modeling of Mitochondrial and Cellular Energy Metabolic Flux Dynamics in Health and Disease.

Mitochondrial respiratory chain (RC) transforms the reductive power of NADH or FADH2 oxidation into a proton gradient between the matrix and cytosolic sides of the inner mitochondrial membrane, that ATP synthase uses to generate ATP. This process constitutes a bridge between carbohydrates' central metabolism and ATP-consuming cellular functions. Moreover, the RC is responsible for a large part of reactive oxygen species (ROS) generation that play signaling and oxidizing roles in cells. Mathematical methods and computational analysis are required to understand and predict the possible behavior of this metabolic system. Here we propose a software tool that helps to analyze individual steps of respiratory electron transport in their dynamics, thus deepening understanding of the mechanism of energy transformation and ROS generation in the RC. This software's core is a kinetic model of the RC represented by a system of ordinary differential equations (ODEs). This model enables the analysis of complex dynamic behavior of the RC, including multistationarity and oscillations. The proposed RC modeling method can be applied to study respiration and ROS generation in various organisms and naturally extended to explore carbohydrates' metabolism and linked metabolic processes.