Regulatory effects of the mitochondrial energetic status on mitochondrial p66Shc.
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.
Orsini
Francesca
F
Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, I-20141 Milan, Italy.
Moroni
Maurizio
M
Contursi
Cristina
C
Yano
Masato
M
Pelicci
PierGiuseppe
P
Giorgio
Marco
M
Migliaccio
Enrica
E
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011485:Protein Binding; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1