Akt Protects Cells from Cytochrome c

Science's STKE  31 Oct 2000:
Vol. 2000, Issue 56, pp. tw9
DOI: 10.1126/stke.2000.56.tw9

Neuronal survival mediated by phosphoinositide 3-kinase activation involves the activation of a downstream kinase Akt. Zhou et al. used hybrid motor neurons transfected with constitutively active Akt to show that overexpression of Akt blocks ceramide-induced apoptosis. Constitutively active Akt did not block the release of cytochrome c into the cytosol; however, it did protect cells from microinjected cytochrome c. This suggests that Akt inhibits apoptosis downstream of cytochrome c, which is released from mitochondria in response to proapoptotic stimuli. Further support for the placement of the antiapoptotic activity of Akt downstream of cytochrome c came from cell-free assays in which Akt inhibited caspase activation and cleavage of poly (ADP ribose) polymerase (PARP) by cytochrome c.

Zhou, H., Li, X.-M., Meinkoth, J., and Pittman, R.A. (2000) Akt regulates cell survival and apoptosis at a postmitochondrial level. J. Cell Biol. 151: 483-494. [Abstract] [Full Text]