Unfolded and misfolded proteins in the endoplasmic reticulum (ER) of eukaryotic cells elicit a highly conserved unfolded protein response (UPR) that leads to an increase in the capacity of the ER to deal with protein folding by hightened expression of enzymes such as chaperone and protein disulfide isomerases. However, cells die by apoptosis if the function of the ER cannot be restored in metazoans. To what extent is this mechanism evolutionarily conserved in plant cells remains to be elucidated. Emerging data from our recent study now provide compelling evidence that a conserved cell death suppressor, BAX inhibitor-1 (BI-1), plays a pivotal role as a survival factor against endoplasmic reticulum stress-mediated programmed cell death (PCD) that likely acts in parallel to the UPR pathway. This finding suggests a clear functional correlation to the predicted ER localization of AtBI1 as well as directly implicating the ER of plant cells as an important modulator of cell death activation. Furthermore, ER stress and its associated cell death in plants can be relieved by administration of chemical chaperones which have been clinically used for treatment of many human diseases linked to neurodegenerative disorders that are triggered by the dysfunction of ER homeostasis. This opens the way for future studies to decipher the mechanisms and pathways of ER-mediated PCD, and function of this pathway in plant development and stress response.
