Interplay between the unfolded protein response and reactive oxygen species: a dynamic duo

Abstract

Secretory proteins undergo modifications such as glycosylation and disulphide bond formation before proper folding, and move to their final destination via the endomembrane system. Accumulation of unfolded proteins in the endoplasmic reticulum (ER) due to suboptimal environmental conditions triggers a response called the unfolded protein response (UPR), which induces a set of genes that elevate protein folding capacity in the ER. This review aims to establish a connection among ER stress, UPR, and reactive oxygen species (ROS), which remains an unexplored topic in plants. For this, we focused on mechanisms of ROS production originating from ER stress, the interaction between ER stress and overall ROS signalling process in the cell, and the interaction of ER stress with other organellar ROS signalling pathways such as of the mitochondria and chloroplasts. The roles of the UPR during plant hormone signalling and abiotic and biotic stress responses are also discussed in connection with redox and ROS signalling.

Isoliquiritigenin Pretreatment Induces Endoplasmic Reticulum Stress-Mediated Hormesis and Attenuates Cisplatin-Induced Oxidative Stress and Damage in LLC-PK1 Cells

“…However, excessive quantities of ROS can result in damage to proteins, modifying their function and disrupting ER homeostasis [ 27 , 32 , 34 , 73 ]. ROS overproduction can be sensed by the ER, which is highly sensitive to changes in ROS levels through redox sensors, such as, for example, the thiol groups of cysteines [ 33 , 70 , 74 , 75 , 76 , 77 ], causing misfolded protein accumulation and consequently increasing ROS production, which leads to a vicious cycle able to activate UPR, generate chronic stress, and induce apoptosis [ 32 , 33 , 34 , 70 , 72 ]. Moreover, ROS overproduction causes a decrease in the GSH/GSSG ratio and in antioxidant enzyme levels, whilst oxidizing lipids, DNA, and proteins [ 19 , 20 , 21 , 22 , 25 , 26 ].…”

“…Under acute ER stress, glucose-related protein 78 kDa (GRP78) and glucose-related protein 94 kDa (GRP94) are released from the ER membrane and activate the unfolded protein response (UPR) to restore ER functions, such as protein synthesis and transport, protein folding, lipid and steroid synthesis, among others [ 27 , 28 , 29 , 30 , 31 ], in addition to the antioxidant response and autophagy [ 27 , 32 , 33 , 34 ], which maintain cellular homeostasis. However, if the ER stress is excessive or chronic and cannot be corrected, UPR signaling promotes apoptosis [ 29 , 31 , 35 , 36 , 37 , 38 , 39 ].…”

Response to Persistent ER Stress in Plants: A Multiphasic Process That Transitions Cells from Prosurvival Activities to Cell Death

“…In mammalian cells, it is said that ER stress and ROS production are in a "vicious cycle" inducing each other (Malhotra and Kaufman, 2007). The situation in plants may be similar to animals (Ozgur et al, 2018), but that requires further testing.…”

ROS‐mediated PERK‐eIF2α‐ATF4 pathway plays an important role in arsenite‐induced L‐02 cells apoptosis via regulating CHOP‐DR5 signaling

“…As well known, ROS mediated‐stress damage is common denominator in arsenic‐induced disease 45 . A series of studies have shown that excessive accumulation of ROS has associated with the ER stress to further aggravate cell death 46‐48 …”