Optineurin modulates ER stress-induced signaling pathways and cell death

We have investigated the physiological role of the autophagy receptor Optineurin/Optn in endoplasmic reticulum (ER) stress response using cellular and animal models. In comparison to their normal counterparts, Optn-deficient mouse embryonic fibroblasts showed significantly higher cell death and caspase-3 activation upon treatment with tunicamycin and thapsigargin, inducers of ER stress. The transcript levels of some of the genes regulated by the IRE1-XBP1 and PERK-ATF4 pathways were upregulated in Optn-deficient cells, in comparison with normal cells, upon treatment with tunicamycin, and also in the brain cortex and liver of tunicamycin treated Optn-deficient mice. Also, the basal levels of IRE1 alpha and PERK were higher in Optn-deficient cells. These results suggest that Optn modulates ER stress-induced signaling pathways and provides protection from ER stress-induced cell death. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The autophagy receptor Optineurin/Optn plays a physiological role in the endoplasmic reticulum stress response, regulating cell death and signaling pathways. Optn deficiency results in higher cell death and caspase-3 activation, while upregulating transcript levels of genes in the IRE1-XBP1 and PERK-ATF4 pathways. This suggests that Optn modulation provides protection against ER stress-induced cell death.