Reversible and irreversible mitochondrial swelling in vitro.

Area of Science:

• Mitochondrial biophysics
• Cellular mechanics
• Biophysical modeling

Background:

• Mitochondrial activity, particularly ATP production, is sensitive to mitochondrial swelling (MS) dynamics.
• Understanding MS is crucial for comprehending mitochondrial function and dysfunction.
• Previous models lacked detailed biophysical mechanisms for solute transport and membrane mechanics.

Purpose of the Study:

• To develop a detailed biophysical model of reversible and irreversible mitochondrial swelling (MS).
• To incorporate the mechanical properties of the inner mitochondrial membrane (IMM) into the MS model.
• To determine transition criteria between reversible and irreversible MS and predict system behavior.

Main Methods:

• Developed a detailed biophysical model describing MS dynamics for various mitochondrial shapes (spherical, ellipsoidal).
• Incorporated mechanical properties of the IMM using a second-rank rigidity tensor, fitting to in vitro experimental data.
• Included membrane bending effects and detailed ionic/neutral solute transport mechanisms.

Main Results:

• Estimated IMM rigidity constant at approximately 0.008 dyn/nm for linear deformations.
• Successfully simulated previously reported experimental data and predicted system behavior under different initial conditions.
• Determined and validated criteria for the transition from reversible to irreversible swelling.

Conclusions:

• The developed model provides a deeper understanding of MS mechanisms and the transition to irreversible swelling.
• The model offers valuable mathematical tools for mitochondrial biophysics research and predicting mitochondrial behavior in vitro.
• The model suggests a physically consistent mechanism for permeability transition pore (PTP) opening dependent on IMM stretching stress.