Pathways for Sensing and Responding to Hydrogen Peroxide at the Endoplasmic Reticulum

The endoplasmic reticulum (ER) has emerged as a source of hydrogen peroxide (H(2)O(2)) and a hub for peroxide-based signaling events. Here we outline cellular sources of ER-localized peroxide, including sources within and near the ER. Focusing on three ER-localized proteins—the molecular chaperone BiP, the transmembrane stress-sensor IRE1, and the calcium pump SERCA2—we discuss how post-translational modification of protein cysteines by H(2)O(2) can alter ER activities. We review how changed activities for these three proteins upon oxidation can modulate signaling events, and also how cysteine oxidation can serve to limit the cellular damage that is most often associated with elevated peroxide levels.