Computational modeling of In vitro swelling of mitochondria: A biophysical approach
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/11077 |
Resumo: | 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. |
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Computational modeling of In vitro swelling of mitochondria: A biophysical approachPermeability Transition PoreInner MembraneAtp SynthaseCell-DeathMathematical-ModelCalcium UniporterChannelOscillationsHeartCa2+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.National 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]MDPISapientiaMakarov, Vladimir I.Khmelinskii, IgorJavadov, Sabzali2018-12-07T14:52:25Z2018-042018-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11077eng1420-304910.3390/molecules23040783info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:22:49Zoai:sapientia.ualg.pt:10400.1/11077Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:02:36.469237Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
title |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
spellingShingle |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach Makarov, Vladimir I. Permeability Transition Pore Inner Membrane Atp Synthase Cell-Death Mathematical-Model Calcium Uniporter Channel Oscillations Heart Ca2+ |
title_short |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
title_full |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
title_fullStr |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
title_full_unstemmed |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
title_sort |
Computational modeling of In vitro swelling of mitochondria: A biophysical approach |
author |
Makarov, Vladimir I. |
author_facet |
Makarov, Vladimir I. Khmelinskii, Igor Javadov, Sabzali |
author_role |
author |
author2 |
Khmelinskii, Igor Javadov, Sabzali |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Makarov, Vladimir I. Khmelinskii, Igor Javadov, Sabzali |
dc.subject.por.fl_str_mv |
Permeability Transition Pore Inner Membrane Atp Synthase Cell-Death Mathematical-Model Calcium Uniporter Channel Oscillations Heart Ca2+ |
topic |
Permeability Transition Pore Inner Membrane Atp Synthase Cell-Death Mathematical-Model Calcium Uniporter Channel Oscillations Heart Ca2+ |
description |
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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-07T14:52:25Z 2018-04 2018-04-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/11077 |
url |
http://hdl.handle.net/10400.1/11077 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1420-3049 10.3390/molecules23040783 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133260769394688 |