Please use this identifier to cite or link to this item:
http://hdl.handle.net/20.500.11889/2694
DC Field | Value | Language |
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dc.contributor.author | Stiban, Johnny | |
dc.contributor.author | Perera, Meenu | |
dc.date.accessioned | 2016-10-15T08:53:32Z | |
dc.date.available | 2016-10-15T08:53:32Z | |
dc.date.issued | 2015 | |
dc.identifier.uri | http://hdl.handle.net/20.500.11889/2694 | |
dc.description.abstract | Mitochondria mediate both cell survival and death. The intrinsic apoptotic pathway is initiated by the permeabilization of the mitochondrial outer membrane to pro-apoptotic inter-membrane space (IMS) proteins. Many pathways cause the egress of IMS proteins. Of particular interest is the ability of ceramide to selfassemble into dynamic water-filled channels. The formation of ceramide channels is regulated extensively by Bcl-2 family proteins and dihydroceramide. Here, we show that the chain length of biologically active ceramides serves as an important regulatory factor. Ceramides are synthesized by a family of six mammalian ceramide synthases (CerS) each of which produces a subset of ceramides that differ in their fatty acyl chain length. Various ceramides permeabilize mitochondria differentially. Interestingly, the presence of very long chain ceramides reduces the potency of C16-mediated mitochondrial permeabilization indicating that the intercalation of the lipids in the dynamic channel has a destabilizing effect, reminiscent of dihydroceramide inhibition of ceramide channel formation (Stiban et al., 2006). Moreover, mitochondria isolated from cells overexpressing the ceramide synthase responsible for the production of C16-ceramide (CerS5) are permeabilized faster upon the exogenous addition of C16-ceramide whereas they are resistant to permeabilization with added C24-ceramide. On the other hand mitochondria isolated from CerS2-overexpressing cells show the opposite pattern, indicating that the product of CerS2 inhibits C16-channel formation ex vivo and vice versa. This interplay between different ceramide metabolic enzymes and their products adds a new dimension to the complexity of mitochondrial-mediated apoptosis, and emphasizes its role as a key regulatory step that commits cells to life or death | |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.subject.lcsh | Saturated fatty acids - Metabolism | |
dc.subject.lcsh | Proteins - Metabolism | |
dc.subject.lcsh | Mitochondrial pathology | |
dc.subject.lcsh | Apoptosis | |
dc.subject.lcsh | Ceramides - Physiological effect | |
dc.title | Very long chain ceramides interfere with C16-ceramide-induced channel formation : a plausible mechanism for regulating the initiation of intrinsic apoptosis | en_US |
newfileds.item-access-type | open_access | en_US |
newfileds.general-subject | Life Sciences and Biology | en_US |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
item.languageiso639-1 | other | - |
Appears in Collections: | Fulltext Publications |
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