Protein Kinase C ß and Prolyl Isomerase 1 Regulate Mitochondrial Effects of the Life-Span Determinant p66 Shc

• DOI: 10.1126/science.1135380
• Publication Date: 2007-02-03T07:58:48Z
• Authors: Paolo Pinton; Alessandro Rimessi; Saverio Marchi; Francesca Orsini; Enrica Migliaccio; Marco Giorgio; Cristina Contursi; Saverio Minucci; Fiamma Mantovani; Mariusz R. Wiecko...; Giannino Del Sal; Pier Giuseppe Pel...; Rosario Rizzuto
• Keywords: 0301 basic medicine; Cell Survival; Apoptosis; Permeability; Mice; 03 medical and health sciences; Pin1; Adenosine Triphosphate; endoplasmic-reticulum ; oxidative stress ; CA2+ signals ; apoptosis ; mechanism; Animals; Calcium Signaling; Phosphorylation; Cells, Cultured; Cellular Senescence; Protein Kinase C; Adaptor Proteins, Signal Transducing; 0303 health sciences; aging; mitochondria; cell death; aging; p66-shc; Hydrogen Peroxide; Peptidylprolyl Isomerase; Mitochondria; mitochondria; NIMA-Interacting Peptidylprolyl Isomerase; Oxidative Stress; Mutation; Cyclosporine; Calcium; Pin1; aging; mitochondria; p66-shc

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