Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization.

Hdl Handle:
http://hdl.handle.net/10147/93851
Title:
Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization.
Authors:
Gupta, Sanjeev; Cuffe, Lorraine; Szegezdi, Eva; Logue, Susan E; Neary, Catherine; Healy, Sandra; Samali, Afshin
Affiliation:
Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland.
Citation:
Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization. 2010, 2010:170215 Int J Cell Biol
Journal:
International journal of cell biology
Issue Date:
2010
URI:
http://hdl.handle.net/10147/93851
DOI:
10.1155/2010/170215
PubMed ID:
20169117
Abstract:
During apoptosis, the process of mitochondrial outer membrane permeabilization (MOMP) represents a point-of-no-return as it commits the cell to death. Here we have assessed the role of caspases, Bcl-2 family members and the mitochondrial permeability transition pore on ER stress-induced MOMP and subsequent cell death. Induction of ER stress leads to upregulation of several genes such as Grp78, Edem1, Erp72, Atf4, Wars, Herp, p58ipk, and ERdj4 and leads to caspase activation, release of mitochondrial intermembrane proteins and dissipation of mitochondrial transmembrane potential (DeltaPsim). Mouse embryonic fibroblasts (MEFs) from caspase-9, -2 and, -3 knock-out mice were resistant to ER stress-induced apoptosis which correlated with decreased processing of pro-caspase-3 and -9. Furthermore, pretreatment of cells with caspase inhibitors (Boc-D.fmk and DEVD.fmk) attenuated ER stress-induced loss of DeltaPsim. However, only deficiency of caspase-9 and -2 could prevent ER stress-mediated loss of DeltaPsim. Bcl-2 overexpression or pretreatment of cells with the cell permeable BH4 domain (BH4-Tat) or the mitochondrial permeability transition pore inhibitors, bongkrekic acid or cyclosporine A, attenuated the ER stress-induced loss of DeltaPsim. These data suggest a role for caspase-9 and -2, Bcl-2 family members and the mitochondrial permeability transition pore in loss of mitochondrial membrane potential during ER stress-induced apoptosis.
Language:
en
ISSN:
1687-8884

Full metadata record

DC FieldValue Language
dc.contributor.authorGupta, Sanjeeven
dc.contributor.authorCuffe, Lorraineen
dc.contributor.authorSzegezdi, Evaen
dc.contributor.authorLogue, Susan Een
dc.contributor.authorNeary, Catherineen
dc.contributor.authorHealy, Sandraen
dc.contributor.authorSamali, Afshinen
dc.date.accessioned2010-03-08T13:14:02Z-
dc.date.available2010-03-08T13:14:02Z-
dc.date.issued2010-
dc.identifier.citationMechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization. 2010, 2010:170215 Int J Cell Biolen
dc.identifier.issn1687-8884-
dc.identifier.pmid20169117-
dc.identifier.doi10.1155/2010/170215-
dc.identifier.urihttp://hdl.handle.net/10147/93851-
dc.description.abstractDuring apoptosis, the process of mitochondrial outer membrane permeabilization (MOMP) represents a point-of-no-return as it commits the cell to death. Here we have assessed the role of caspases, Bcl-2 family members and the mitochondrial permeability transition pore on ER stress-induced MOMP and subsequent cell death. Induction of ER stress leads to upregulation of several genes such as Grp78, Edem1, Erp72, Atf4, Wars, Herp, p58ipk, and ERdj4 and leads to caspase activation, release of mitochondrial intermembrane proteins and dissipation of mitochondrial transmembrane potential (DeltaPsim). Mouse embryonic fibroblasts (MEFs) from caspase-9, -2 and, -3 knock-out mice were resistant to ER stress-induced apoptosis which correlated with decreased processing of pro-caspase-3 and -9. Furthermore, pretreatment of cells with caspase inhibitors (Boc-D.fmk and DEVD.fmk) attenuated ER stress-induced loss of DeltaPsim. However, only deficiency of caspase-9 and -2 could prevent ER stress-mediated loss of DeltaPsim. Bcl-2 overexpression or pretreatment of cells with the cell permeable BH4 domain (BH4-Tat) or the mitochondrial permeability transition pore inhibitors, bongkrekic acid or cyclosporine A, attenuated the ER stress-induced loss of DeltaPsim. These data suggest a role for caspase-9 and -2, Bcl-2 family members and the mitochondrial permeability transition pore in loss of mitochondrial membrane potential during ER stress-induced apoptosis.-
dc.language.isoenen
dc.titleMechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization.en
dc.contributor.departmentApoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway, Ireland.en
dc.identifier.journalInternational journal of cell biologyen

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