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Stretching tension effects in permeability transition pores of inner mitochondrial membrane

dc.contributor.authorKhmelinskii, Igor
dc.contributor.authorMakarov, Vladimir
dc.date.accessioned2021-10-01T10:31:55Z
dc.date.available2021-10-01T10:31:55Z
dc.date.issued2021
dc.description.abstractPresently a mechanism of permeability transition pore (PTP) opening was proposed and discussed. This mechanism is based on mechanical stretching of inner mitochondrial membrane (IMM) caused by mitochondrial swelling (MS). The latter is induced by osmotic pressure generated by solute imbalance between the matrix and the surrounding cyto(sarco)plasm. Modelled by the Monte-Carlo method, an IMM fragment of 350 simulated biological molecules exhibited formation of micro-domains containing two protein and seven phospholipid molecules. The energies (-0.191 eV per molecule) in these micro-domains were significantly larger than those (-0.375 eV per molecule) of other parts of the IMM fragment. Stretching forces applied to such domains expanded them much more than other parts of the IMM fragment. We identify these micro-domains as the PTPs. Both linear and nonlinear functions were used for the strain-stress relation of the IMM fragment, with nonlinear effects more important at large IMM stretching strains. Thus, two main factors are incorporated into the PTP opening mechanism: (1) presence of micro-domains in the IMM structure and (2) IMM stretching stress caused by MS. Taking into account both of these factors, the equation for the probability of PTP opening was deduced, with matrix Ca2+ and H+ ionic concentrations as its parameters. Note that the equation deduced was similar to an earlier reported empirical equation describing PTP opening dynamics. This correspondence provides support to the presently proposed mechanism. Thus, a new look at the PTP opening mechanism is provided, of interest to various research areas related to mitochondrial biophysics.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.biosystems.2021.104488pt_PT
dc.identifier.issn0303-2647
dc.identifier.urihttp://hdl.handle.net/10400.1/17180
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectInner mitochondrial membrane (IMM)pt_PT
dc.subjectSwellingpt_PT
dc.subjectMonte-Carlo simulationspt_PT
dc.subjectMicro-domainpt_PT
dc.subjectPermeability transition pore (PTP) openingpt_PT
dc.titleStretching tension effects in permeability transition pores of inner mitochondrial membranept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage104488pt_PT
oaire.citation.titleBiosystemspt_PT
oaire.citation.volume208pt_PT
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.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationfcb9f09f-2e99-41fb-8c08-7e1acbc65076
relation.isAuthorOfPublication.latestForDiscoveryfcb9f09f-2e99-41fb-8c08-7e1acbc65076

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