BCL-2 family: integrating stress responses at the ER to control cell demise

• Published in: Cell death and differentiation Vol. 24; no. 9; pp. 1478 - 1487
• Main Authors: Pihán, Philippe, Carreras-Sureda, Amado, Hetz, Claudio
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2017
• Subjects: Adapter proteins; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Autophagy; Autophagy - genetics; Autophagy - physiology; Bcl-2 protein; Bioenergetics; Calcium (mitochondrial); Calcium Signaling - genetics; Calcium Signaling - physiology; Calcium signalling; Cell death; Cell fate; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Enzymes; Homeostasis; Humans; Kinases; Mitochondria; Neurosciences; Phagocytosis; Protein folding; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Regulation; Review; Unfolded Protein Response - genetics; Unfolded Protein Response - physiology
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2017.82

In the last decade, the endoplasmic reticulum (ER) has emerged as a central organelle regulating the core mitochondrial apoptosis pathway. At the ER membrane, a variety of stress signals are integrated toward determining cell fate, involving a complex cross talk between key homeostatic pathways including the unfolded protein response, autophagy, calcium signaling and mitochondrial bioenergetics. In this context, key regulators of cell death of the BCL-2 and TMBIM/BI-1 family of proteins have relevant functions as stress rheostats mediated by the formation of distinct protein complexes that regulate the switch between adaptive and proapoptotic phases under stress. Here, we overview recent advances on our molecular understanding of how the apoptotic machinery integrates stress signals toward cell fate decisions upstream of the mitochondrial gateway of death.