Mathematical Modeling Unveils a New Role for Transient Mitochondrial Permeability Transition in ROS Damage Prevention.

We have previously shown that the mitochondrial respiratory chain (RC) can switch between the following two states: (i) an "ATP-producing" state characterized by the low production of reactive oxygen species (ROS), the vigorous translocation of hydrogen ions (H), and the storage of energy from the H gradient in the form of ATP, and (ii) an "ROS-producing" state, where the translocation of H is slow but the production of ROS is high. Here, we suggest that the RC transition from an ATP-producing to an ROS-producing state initiates a mitochondrial permeability transition (MPT) by generating a burst of ROS. Numerous MPT activators induce the transition of the RC to an ROS-producing state, and the ROS generated in this state activate the MPT.