Focal oxidant and Ras signaling on the ER surface activates autophagy.

Eukaryotic cells react to a variety of intrinsic and extrinsic stresses with patterned responses, each triggered within relevant subcellular domains. One feature common to a variety of cellular stresses is the production of reactive oxidant species (ROS), suggesting an additional element of oxidative stress. We addressed the role of oxidants in ER stress and find instead that localized production of ROS by the ER mediates protective signaling, leading to, among other things, Ras-dependent activation of autophagy. Thus, focal oxidant production is incorporated into stress response pathways, in this case participating in homeostatic signaling circuits on the ER surface.