Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.bpj.2010.09.041
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dc.titleElucidating cytochrome c release from mitochondria: Insights from an in silico three-dimensional model
dc.contributor.authorTam, Z.Y.
dc.contributor.authorCai, Y.H.
dc.contributor.authorGunawan, R.
dc.date.accessioned2014-06-17T07:39:55Z
dc.date.available2014-06-17T07:39:55Z
dc.date.issued2010-11-17
dc.identifier.citationTam, Z.Y., Cai, Y.H., Gunawan, R. (2010-11-17). Elucidating cytochrome c release from mitochondria: Insights from an in silico three-dimensional model. Biophysical Journal 99 (10) : 3155-3163. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bpj.2010.09.041
dc.identifier.issn00063495
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/63821
dc.description.abstractMitochondrial regulation of apoptosis depends on the programmed release of proapoptotic proteins such as cytochrome c (Cyt c) through the outer mitochondrial membrane (OMM). Although a few key processes involved in this release have been identified, including the liberation of inner membrane-bound Cyt c and formation of diffusible pores on the OMM, other details like the transport of Cyt c within complex mitochondrial compartments, e.g., the cristae and crista junctions, are not yet fully understood (to our knowledge). In particular, a remodeling of the inner mitochondrial membrane accompanying apoptosis seen in a few studies, in which crista junctions widen, has been hypothesized to be a necessary step in the Cyt c release. Using a three-dimensional spatial modeling of mitochondrial crista and the crista junction, model simulations and analysis illustrated how the interplay among solubilization of Cyt c, fast diffusion of Cyt c, and OMM permeabilization gives rise to the observed experimental release profile. Importantly, the widening of the crista junction was found to have a negligible effect on the transport of free Cyt c from cristae. Finally, model simulations showed that increasing the fraction of free/loosely-bound Cyt c can sensitize the cell to apoptotic stimuli in a threshold manner, which may explain increased sensitivity to cell death associated with aging. © 2010 by the Biophysical Society.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.bpj.2010.09.041
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCHEMICAL & BIOMOLECULAR ENGINEERING
dc.description.doi10.1016/j.bpj.2010.09.041
dc.description.sourcetitleBiophysical Journal
dc.description.volume99
dc.description.issue10
dc.description.page3155-3163
dc.description.codenBIOJA
dc.identifier.isiut000284438700008
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