Regulatory effects of the mitochondrial energetic status on mitochondrial p66Shc.

Biol Chem 2006 Oct-Nov;387(10-11):1405-10

Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, I-20141 Milan, Italy.

p66(Shc) promotes apoptosis and controls the intracellular redox balance. A fraction of p66(Shc) 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 p66(Shc) 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 p66(Shc) activation, which highlight the energetic status of mitochondria as a crucial determinant of p66(Shc) function.

Download full-text PDF

Source
http://dx.doi.org/10.1515/BC.2006.176DOI Listing
December 2006

Publication Analysis

Top Keywords

energetic status
8
p66shc
8
p66shc expression
4
tolerate p66shc
4
cells tolerate
4
role mitochondrial
4
expression accumulate
4
oxidative damage
4
accumulate oxidative
4
investigations role
4
mitochondrial import
4
apoptosis cells
4
import machinery
4
induces mitochondrial
4
turn induces
4
mitochondrial permeability
4
peroxide turn
4
novel investigations
4
permeability apoptosis
4
protein stabilization
4

Similar Publications