Arabidopsis thaliana tolerance to cadmium stress is mediated by endoplasmic reticulum stress sensing.

About one third of all Eukaryotic proteins are folded and glycosylated in the Endoplasmic Reticulum (ER) under the control of a sophisticated machinery called Endoplasmic Reticulum Quality Control (ERQC), which ensures only properly folded glycoproteins can reach their final secretory destination. By contrast, glycoproteins that are not able to attain their intended fold are degraded by a second ER-resident machinery, called ER-Associated Degradation (ERAD). The ER homeostatic balance between glycoprotein folding capacity and glycoprotein folding demand is strictly controlled by the cell, because accumulation of misfolded glycoproteins in the ER is an important cause of cell stress. In this context, all eukaryotic genomes also encode the components of the Unfolded Protein Response (UPR) signalling pathway with the aim to restore glycoprotein homeostasis by reducing (mis)folded glycoprotein accumulation in the ER and guarantee cell survival. When ER stress is severe, UPR can also trigger programmed cell death (PCD). UPR activation has been studied in plants in response to several biotic and abiotic stresses, but knowledge about its role in response to heavy metal stress is fairly limited, since the regulation of UPR key genes expression depends specifically on the stress applied. For example, the Arabidopsis thaliana (A. thaliana) double mutant Atbzip28/bzip60, lacking the two main transcription factors (TFs) involved in UPR activation, shows higher tolerance to heavy metals, but a higher sensitivity to tunicamycin and biotic stresses. These results highlight the variegated and complex regulation of UPR. In this work, we studied the effects of chronic and temporary cadmium (Cd) treatment on ER stress using A. thaliana as a model system. In detail, we used: (i) Wt plants to investigate the consequences of plant exposure to Cd on the ERQC, ERAD, UPR and PCD pathways; (ii) Atbzip28/bzip60 double mutant plants to monitor the consequences of down-regulation of UPR genes on the ERQC, ERAD and PCD pathways. Our data clearly suggest that ER stress is part of the A. thaliana response to Cd and that this response varies with stress time and heavy metal concentration. Cd treatment leads to an upregulation of key ERQC and UPR genes, also it modulates the induction of PCD pathway when the ER stress is severe, with the upregulation of the membrane-associated transcription factor NAC089. Conversely, Cd treatment did not greatly impact on ERAD and UPR marker genes in the Atbzip28/bzip60 double mutant, suggesting a reduced sensitivity of this mutant to Cd induced ER stress. Taken together these results suggest that the modulation of ER stress sensing could be a useful tool to increase crop plants tolerance to Cd.