Regulatory effects of the mitochondrial energetic status on mitochondrial p66Shc

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 p66 Shc 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 p66 Shc 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 p66 Shc function. Copyright