Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization
Joint Authors
Samali, Afshin
Logue, Susan E.
Gupta, Sanjeev
Cuffe, Lorraine
Neary, Catherine
Healy, Sandra
Szegezdi, Eva
Source
International Journal of Cell Biology
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-02-07
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
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 (ΔΨm).
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 ΔΨm.
However, only deficiency of caspase-9 and -2 could prevent ER stress-mediated loss of ΔΨm.
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 ΔΨm.
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.
American Psychological Association (APA)
Gupta, Sanjeev& Cuffe, Lorraine& Szegezdi, Eva& Logue, Susan E.& Neary, Catherine& Healy, Sandra…[et al.]. 2010. Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization. International Journal of Cell Biology،Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-451463
Modern Language Association (MLA)
Gupta, Sanjeev…[et al.]. Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization. International Journal of Cell Biology No. 2010 (2010), pp.1-9.
https://search.emarefa.net/detail/BIM-451463
American Medical Association (AMA)
Gupta, Sanjeev& Cuffe, Lorraine& Szegezdi, Eva& Logue, Susan E.& Neary, Catherine& Healy, Sandra…[et al.]. Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization. International Journal of Cell Biology. 2010. Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-451463
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-451463