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

Federica Di Sano, Elisabetta Ferraro, Roberta Tufi, Tilmann Achsel, Mauro Piacentini, Francesco Cecconi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2693-2700
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number5
DOIs
Publication statusPublished - Feb 3 2006

ASJC Scopus subject areas

  • Biochemistry

Fingerprint

Dive into the research topics of 'Endoplasmic reticulum stress induces apoptosis by an apoptosome-dependent but caspase 12-independent mechanism'. Together they form a unique fingerprint.

Cite this