Reactive oxygen species-mediated apoptosis and endoplasmic reticulum stress pathway (ROS/ER stress pathway)

The Reactive oxygen species (ROS)-mediated apoptosis and endoplasmic reticulum (ER) stress pathway is a complex signaling network where oxidative stress and proteotoxic stress converge to trigger programmed cell death. ROS can directly damage ER-resident proteins or disrupt calcium homeostasis, leading to the accumulation of misfolded proteins and the activation of the Unfolded Protein Response (UPR) (Zeeshan et al., 2016). While the UPR initially serves a cytoprotective role, prolonged or severe stress shifts the balance toward apoptosis through the upregulation of pro-apoptotic factors like CHOP and the activation of JNK and caspases (Malhotra & Kaufman, 2007). This pathway is a significant focus in oncology, where drugs like bortezomib are used to overwhelm the ER's folding capacity in cancer cells to induce death (Obeng et al., 2006). However, its chronic activation is also a key driver of pathology in neurodegenerative diseases and metabolic disorders like diabetes (Ozcan et al., 2006). Therapeutic strategies often involve either inducing this pathway to kill cancer cells or inhibiting its pro-apoptotic components to preserve cell viability in degenerative conditions.

Other names

ROS/ER stress-mediated apoptosisOxidative stress-induced ER stress pathwayUPR-mediated cell death

Induction of excessive intracellular reactive oxygen species (ROS) that disrupts endoplasmic reticulum (ER) homeostasis, leading to the accumulation of misfolded proteins and the activation of the pro-apoptotic Unfolded Protein Response (UPR) signaling cascade.