Fig. 8.

Schematic model of ER stress-induced stress. Details described in text. Cell survival: protein misfolding in the ER is sensed by Ire1 that dimerizes to induce increased transcriptional activation in the nucleus; Ire1 activity is necessary for survival of ER stress. In response to ER stress, MMP and O₂ consumption are increased [by Ca²⁺ influx into mitochondria [3]]. Activation of calcineurin is a requisite event for cell survival [this paper and [31]]. Cell death: protein misfolding in the ER cannot induce a transcriptional response without Ire1. Ca²⁺ flux is abnormal without calcineurin [9]. Genetic evidence suggests Ca²⁺ homeostasis is also dysregulated in ire1∆ cells. In both cnb1∆ and ire1∆ cells, MMP and O₂ consumption fail to respond to ER stress, ROS is accumulated and death ensues (Figs. 1 and 3).