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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
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Mathematical Modeling Unveils a New Role for Transient Mitochondrial Permeability Transition in ROS Damage
Olga A Zagubnaya1,2, Vitaly A Selivanov3,4, Mark Pekker5
1Department of Mathematical Modeling and Statistical Analysis, Institute of Cytochemistry and Molecular Pharmacology, Moscow 115404, Russia.
Cells
|July 11, 2025
Summary
The mitochondrial respiratory chain switches between ATP production and ROS production. A transient mitochondrial permeability transition, triggered by ROS, protects cells from oxidative stress.
Area of Science:
- Mitochondrial biology
- Cellular respiration
- Oxidative stress
Background:
- The mitochondrial respiratory chain (RC) exists in two states: ATP-producing (low ROS, high H+ translocation) and ROS-producing (high ROS, low H+ translocation).
- Reactive oxygen species (ROS) play a role in cellular signaling and damage.
Purpose of the Study:
- To investigate the role of the RC's transition to an ROS-producing state in initiating mitochondrial permeability transition (MPT).
- To elucidate the feedback mechanism between ROS production, MPT, and RC state.
- To model glutamate-induced RC and MPT dynamics in nervous tissue.
Main Methods:
- Observational studies on RC states and MPT activators.
- Analysis of ROS generation during RC state transitions.
- Development of a computational model for glutamate and ROS dynamics.
Main Results:
- The transition of the RC to an ROS-producing state initiates MPT via ROS burst.
- MPT activation leads to RC returning to an ATP-producing state, preventing sustained ROS damage.
- Glutamate overload was shown to induce the RC to switch to an ROS-producing state, subsequently activating MPT.
Conclusions:
- Transient MPT acts as a protective mechanism against oxidative stress by regulating RC states.
- The interplay between RC states, ROS, and MPT is crucial for cellular homeostasis.
- The developed model accurately predicts spatial-temporal dynamics of glutamate and H2O2 in nervous tissue.
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