Regulatory effects of the mitochondrial energetic status on mitochondrial p66Shc

• Published in: Biological chemistry Vol. 387; no. 10/11; pp. 1405 - 1410
• Main Authors: Orsini, Francesca, Moroni, Maurizio, Contursi, Cristina, Yano, Masato, Pelicci, PierGiuseppe, Giorgio, Marco, Migliaccio, Enrica
• Format: Journal Article
• Language: English
• Published: Germany Walter de Gruyter 01.10.2006
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; apoptosis; Cell Line; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Lung - metabolism; Mice; mitochondria; Mitochondria - metabolism; Myocardium - metabolism; Protein Binding; reactive oxygen species; Shc Signaling Adaptor Proteins; Src Homology 2 Domain-Containing, Transforming Protein 1
• ISSN: 1431-6730; 1437-4315
• DOI: 10.1515/BC.2006.176

p66Shc promotes apoptosis and controls the intracellular redox balance. A fraction of p66Shc exists within mitochondria, where it oxidizes cytochrome c to form hydrogen peroxide, which in turn induces mitochondrial permeability and apoptosis. However, cells tolerate p66Shc expression and accumulate oxidative damage under normal conditions, implying that the p66Shc functions must be tightly regulated. Here we review available knowledge on the regulation of p66Shc transcription, protein stabilization and post-translational modifications. In addition, we report novel investigations into the role of the mitochondrial import machinery on p66Shc activation, which highlight the energetic status of mitochondria as a crucial determinant of p66Shc function.