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.

DI SANO, F., Ferraro, E., Tufi, R., Achsel, T., Piacentini, M., Cecconi, F. (2006). Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(5), 2693-2700 [10.1074/jbc.M509110200].

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

DI SANO, FEDERICA;PIACENTINI, MAURO;CECCONI, FRANCESCO
2006-02-03

Abstract

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.
3-feb-2006
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
English
Con Impact Factor ISI
Animals; Apoptotic Protease-Activating Factor 1; Apoptosis; Calcium; Endoplasmic Reticulum; Intracellular Signaling Peptides and Proteins; Apoptosis Regulatory Proteins; Caspase 12; Mice; Caspases; Transcription Factor CHOP; Oxidative Stress; Proteins; Mitochondrial Proteins; Molecular Chaperones; Heat-Shock Proteins
DI SANO, F., Ferraro, E., Tufi, R., Achsel, T., Piacentini, M., Cecconi, F. (2006). Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(5), 2693-2700 [10.1074/jbc.M509110200].
DI SANO, F; Ferraro, E; Tufi, R; Achsel, T; Piacentini, M; Cecconi, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39081
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