The endoplasmic reticulum (ER) stress response is triggered by any condition that disrupts protein folding and promotes the accumulation of unfolded proteins in the lumen of the organelle. In eukaryotic cells, the evolutionarily conserved unfolded protein response is activated to clear unfolded proteins and restore ER homeostasis. The recovery from ER stress is accomplished by decreasing protein translation and loading into the organelle, increasing the ER protein processing capacity and ER-associated protein degradation activity. However, if the ER stress persists and cannot be reversed, the chronically prolonged stress leads to cellular dysfunction that activates cell death signaling as an ultimate attempt to survive. Accumulating evidence implicates ER stress-induced cell death signaling pathways as significant contributors for stress adaptation in plants, making modulators of ER stress pathways potentially attractive targets for stress tolerance engineering. Here, we summarize recent advances in understanding plant-specific molecular mechanisms that elicit cell death signaling from ER stress. We also highlight the conserved features of ER stress-induced cell death signaling in plants shared by eukaryotic cells.

Any condition that disrupts the ER homeostasis activates a cytoprotective signaling cascade, designated as the unfolded protein response (UPR), which is transduced in plant cells by a bipartite signaling module. Activation of IRE1/ bZIP60 and bZIP28/bZIP17, which represent the bipartite signaling arms and serve as ER stress sensors and transducers, results in the upregulation of ER protein processing machinery-related genes to recover from stress. However, if the ER stress persists and the cell is unable to restore ER homeostasis, programmed cell death signaling pathways are activated for survival. Here, we describe an ER stress-induced plant-specific cell death program, which is a shared response to multiple stress signals. This signaling pathway was first identified through genome-wide expression profile of differentially expressed genes in response to combined ER stress and osmotic stress. Among them, the development and cell death domain-containing N-rich proteins (DCD/NRPs), NRP-A and NRP-B, and the transcriptional factor GmNAC81 were selected as mediators of cell death in plants. These genes were used as targets to identify additional components of the cell death pathway, which is described here as a regulatory circuit that integrates a stress-induced cell death program with leaf senescence via the NRP-A/NRP-B/GmNAC81:GmNAC30/VPE signaling module.