Journal
SCIENCE SIGNALING
Volume 8, Issue 382, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aaa0341
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science
- Uehara Memorial Foundation
- NIH [HL107594, DK067493, DK020579]
- Department of Veterans Affairs [I01BX000448, I01BX001969]
- Diabetes Research Foundation [17-2013-512]
- American Diabetes Association [1-12-CT-61]
- Ellie White Foundation for Rare Genetic Disorders
- Jack and JT Snow Scientific Research Foundation
- Team Ian
- Team Alejandro
Ask authors/readers for more resources
The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IRE1 signaling prevented ER membrane permeabilization mediated by Bax and Bak and cell death in cells experiencing ER stress. Suppression of IRE1 signaling triggered by its kinase activity led to the accumulation of the BH3 domain-containing protein Bnip3, which in turn triggered the oligomerization of Bax and Bak in the ER membrane and ER membrane permeabilization. Consequently, in response to ER stress, cells deficient in IRE1 were susceptible to leakage of ER contents, which was associated with the accumulation of calcium in mitochondria, oxidative stress in the cytosol, and ultimately cell death. Our results reveal a role for IRE1 in preventing a cell deathinitializing step that emanates from the ER and provide a potential target for treating diseases characterized by ER stress, including diabetes and Wolfram syndrome.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available