+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism



Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism



Journal of Biological Chemistry 281(5): 2693-2700



The endoplasmic reticulum (ER) is the cellular site of polypeptide folding and modification. When these processes are hampered, an unfolded protein response (UPR) is activated. If the damage is too broad, the mammalian UPR launches the apoptotic program. As a consequence, mobilization of ER calcium stores sensitizes mitochondria to direct proapoptotic stimuli. We make use of a mouse Apaf1-deficient cell system of proneural origin to understand the roles played in this context by the apoptosome, the most studied apoptotic machinery along the mitochondrial pathway of death. We show here that in the absence of the apoptosome ER stress induces cytochrome c release from the mitochondria but that apoptosis cannot occur. Under these circumstances, Grp78/BiP and GADD153/CHOP, both hallmarks of UPR, are canonically up-regulated, and calcium is properly released from ER stores. We also demonstrate that caspase 12, a protease until now believed to play a central role in the initiation of ER stress-induced cell death in the mouse system, is dispensable for the mitochondrial pathway of death to take place.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 012036645

Download citation: RISBibTeXText

PMID: 16317003

DOI: 10.1074/jbc.m509110200


Related references

Endoplasmic reticulum stress-induced apoptosis in Leishmania through Ca2+-dependent and caspase-independent mechanism. Journal of Biological Chemistry 286(15): 13638-13646, 2011

Atrazine induces endoplasmic reticulum stress-mediated apoptosis of T lymphocytes via the caspase-8-dependent pathway. Environmental Toxicology 31(8): 998, 2016

An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. Journal of Biological Chemistry 277(37): 34287-34294, 2002

Mollugin induces apoptosis in human Jurkat T cells through endoplasmic reticulum stress-mediated activation of JNK and caspase-12 and subsequent activation of mitochondria-dependent caspase cascade regulated by Bcl-xL. Toxicology and Applied Pharmacology 241(2): 210-220, 2009

Bufalin Induces Apoptosis of Human Osteosarcoma U-2 OS Cells through Endoplasmic Reticulum Stress, Caspase- and Mitochondria-Dependent Signaling Pathways. Molecules 22(3):, 2017

7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway. Molecular Genetics and Metabolism Reports 10: 56-60, 2017

Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. Journal of Biological Chemistry 280(33): 29578-29587, 2005

Influenza induces endoplasmic reticulum stress, caspase-12-dependent apoptosis, and c-Jun N-terminal kinase-mediated transforming growth factor-β release in lung epithelial cells. American Journal of Respiratory Cell and Molecular Biology 46(5): 573-581, 2012

Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress and induces caspase-dependent cell death in antiestrogen-sensitive and resistant ER+ breast cancer cells. Autophagy 6(1): 19-35, 2010

PEP-1-glutaredoxin-1 induces dedifferentiation of rabbit articular chondrocytes by the endoplasmic reticulum stress-dependent ERK-1/2 pathway and the endoplasmic reticulum stress-independent p38 kinase and PI-3 kinase pathways. International Journal of Biological Macromolecules 111: 1059-1066, 2018

Bursopentin (BP5) induces G1 phase cell cycle arrest and endoplasmic reticulum stress/mitochondria-mediated caspase-dependent apoptosis in human colon cancer HCT116 cells. Cancer Cell International 19: 130, 2019

Influenza Induces Endoplasmic Reticulum Stress, Caspase-12-Dependent Apoptosis, and c-Jun N-Terminal Kinase-Mediated Transforming Growth Factor-beta Release in Lung Epithelial Cells. 2012

Na/Ca exchanger overexpression induces endoplasmic reticulum stress, caspase-12 release, and apoptosis. Annals of the new York Academy of Sciences 1010: 430-432, 2003

Mcl-1 reduction due to caspase-dependent cleavage during endoplasmic reticulum stress-induced apoptosis. Journal of Biological Chemistry 286(44): Le24; Author Reply Le25, 2011

Endoplasmic reticulum stress induces a caspase-dependent N-terminal cleavage of RBX1 protein in B cells. Journal of Biological Chemistry 287(37): 31223-31232, 2012