American Association for the Advancement of Science, Science, 5812(315), p. 659-663, 2007
Full text: Download
The 66-kilodalton isoform of the growth factor adapter Shc (p66 Shc ) translates oxidative damage into cell death by acting as reactive oxygen species (ROS) producer within mitochondria. However, the signaling link between cellular stress and mitochondrial proapoptotic activity of p66 Shc was not known. We demonstrate that protein kinase C β, activated by oxidative conditions in the cell, induces phosphorylation of p66 Shc and triggers mitochondrial accumulation of the protein after it is recognized by the prolyl isomerase Pin1. Once imported, p66 Shc causes alterations of mitochondrial Ca 2+ responses and three-dimensional structure, thus inducing apoptosis. These data identify a signaling route that activates an apoptotic inducer shortening the life span and could be a potential target of pharmacological approaches to inhibit aging.