ER stress responses in the absence of apoptosome: A comparative study in CASP9 proficient vs deficient mouse embryonic fibroblasts

• Apoptosome affects UPR kinetics.
• Absence of apoptosome induces more robust autophagy response.
• Lack of apoptosome activates an alternative cell death pathway.

Cells respond to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR), autophagy and cell death. In this study we utilized casp9+/+ and casp9−/− MEFs to determine the effect of inhibition of mitochondrial apoptosis pathway on ER stress-induced-cell death, UPR and autophagy. We observed prolonged activation of UPR and autophagy in casp9−/− cells as compared with casp9+/+ MEFs, which displayed transient activation of both pathways. Furthermore we showed that while casp9−/− MEFs were resistant to ER stress, prolonged exposure led to the activation of a non-canonical, caspase-mediated mode of cell death.