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Molecules 2018, 23(4), 783; https://doi.org/10.3390/molecules23040783

Computational Modeling of In Vitro Swelling of Mitochondria: A Biophysical Approach

1
Department of Physics, University of Puerto Rico, Rio Piedras Campus, San Juan, PR 00931-3343, USA
2
Faculty of Sciences and Technology, Department of Chemistry and Pharmacy, and Interdisciplinary Centre of Chemistry of Algarve, University of Algarve, 8005-139 Faro, Portugal
3
Department of Physiology and Biophysics, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936-5067, USA
*
Author to whom correspondence should be addressed.
Received: 22 February 2018 / Revised: 12 March 2018 / Accepted: 27 March 2018 / Published: 28 March 2018
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Abstract

Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the colloid osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling is important for simulation and prediction of in vivo events in the cell during oxidative and energy stress. In the present study, we developed a computational model that describes the mechanism of mitochondrial swelling based on osmosis, the rigidity of the IMM, and dynamics of ionic/neutral species. The model describes a new biophysical approach to swelling dynamics, where osmotic pressure created in the matrix is compensated for by the rigidity of the IMM, i.e., osmotic pressure induces membrane deformation, which compensates for the osmotic pressure effect. Thus, the effect is linear and reversible at small membrane deformations, allowing the membrane to restore its normal form. On the other hand, the membrane rigidity drops to zero at large deformations, and the swelling becomes irreversible. As a result, an increased number of dysfunctional mitochondria can activate mitophagy and initiate cell death. Numerical modeling analysis produced results that reasonably describe the experimental data reported earlier. View Full-Text
Keywords: mitochondria; biophysical modeling; mitochondrial swelling; permeability transition pore; kinetic analysis; matrix volume; calcium mitochondria; biophysical modeling; mitochondrial swelling; permeability transition pore; kinetic analysis; matrix volume; calcium
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Makarov, V.I.; Khmelinskii, I.; Javadov, S. Computational Modeling of In Vitro Swelling of Mitochondria: A Biophysical Approach. Molecules 2018, 23, 783.

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