Mitochondrial Diversion and Aging

Science's STKE  06 Feb 2007:
Vol. 2007, Issue 372, pp. tw42
DOI: 10.1126/stke.3722007tw42

The protein p66Shc facilitates protein-protein interactions in growth factor signaling pathways. But mutations in Shc can enhance life span in mammals. This effect appears to depend on a different function of Shc whereby it exerts oxidoreductase activity in mitochondria and generates oxygen radicals that lead to cell death. Pinton et al. now show that the activity of Shc in the mitochondria depends on its phosphorylation by protein kinase C β and consequent binding of the prolyl isomerase Pin1. This leads to a conformational change in the protein and to its accumulation in mitochondria. This signaling pathway could provide a target to help delay aging.

P. Pinton, A. Rimessi, S. Marchi, F. Orsini, E. Migliaccio, M. Giorgio, C. Contursi, S. Minucci, F. Mantovani, M. R. Wieckowski, G. Del Sal, P. G. Pelicci, R. Rizzuto, Protein kinase C β and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315, 659-663 (2007). [Abstract] [Full Text]

G. Hajnóczky, J. B. Hoek, Mitochondrial longevity pathways. Science 315, 607-609 (2007). [Summary] [Full Text]