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Cell Death Differ. 2017 Sep;24(9):1478-1487. doi: 10.1038/cdd.2017.82. Epub 2017 Jun 16.

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

Pihán P1,2,3, Carreras-Sureda A1,2,3, Hetz C1,2,3,4,5.

Author information

1
Faculty of Medicine, Biomedical Neuroscience Institute, University of Chile, Santiago, Chile.
2
Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
3
Faculty of Medicine, Center for Geroscience, Brain Health and Metabolism, University of Chile, Santiago, Chile.
4
Buck Institute for Research on Aging, Novato, CA 94945, USA.
5
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston MA 02115, USA.

Abstract

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.

PMID:
28622296
PMCID:
PMC5563989
DOI:
10.1038/cdd.2017.82
[Indexed for MEDLINE]
Free PMC Article

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