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Computational modeling of In vitro swelling of mitochondria: A biophysical approach

2018-04Journal article Open Access
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dc.contributor.authorMakarov, Vladimir I.
dc.contributor.authorKhmelinskii, Igor
dc.contributor.authorJavadov, Sabzali
dc.date.accessioned2018-12-07T14:52:25Z
dc.date.available2018-12-07T14:52:25Z
dc.date.issued2018-04
dc.description.abstractSwelling 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.
dc.description.sponsorshipNational Institute of General Medical Sciences of the National Institutes of Health [SC1GM128210]; Puerto Rico Institute for Functional Nanomaterials (National Science Foundation Grant) [1002410]; National Aeronautics and Space Administration (NASA) Puerto Rico Established Program to Stimulate Competitive Research (EPSCoR) [NNX15AK43A]
dc.identifier.doi10.3390/molecules23040783
dc.identifier.issn1420-3049
dc.identifier.urihttp://hdl.handle.net/10400.1/11077
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.subjectPermeability Transition Pore
dc.subjectInner Membrane
dc.subjectAtp Synthase
dc.subjectCell-Death
dc.subjectMathematical-Model
dc.subjectCalcium Uniporter
dc.subjectChannel
dc.subjectOscillations
dc.subjectHeart
dc.subjectCa2+
dc.titleComputational modeling of In vitro swelling of mitochondria: A biophysical approach
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue4
oaire.citation.startPage783
oaire.citation.titleMolecules
oaire.citation.volume23
person.familyNameKhmelinskii
person.givenNameIgor
person.identifier0000000420541031
person.identifier.ciencia-id0D1A-CB6C-6316
person.identifier.orcid0000-0002-6116-184X
person.identifier.ridC-9587-2011
person.identifier.scopus-author-id6701444934
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublicationfcb9f09f-2e99-41fb-8c08-7e1acbc65076
relation.isAuthorOfPublication.latestForDiscoveryfcb9f09f-2e99-41fb-8c08-7e1acbc65076

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