The Grim Reaper on Autopilot?

Science's STKE  13 Feb 2007:
Vol. 2007, Issue 373, pp. tw52
DOI: 10.1126/stke.3732007tw52

The proteins Bax and Bak are key mediators of cell death signals that function at the mitochondria to promote apoptosis. There is evidence for multiple modes of regulation of Bax and Bak in cells. Some studies have proposed that other members of the Bcl-2 family of proteins interact with and directly activate Bax and Bak--a scenario in which cell survival seems to be the default state of the cell. However, activity of Bax and Bak is also held in check by interaction with prosurvival proteins, and it may be that relief of this inhibition determines the cell's fate. Willis et al. (see the Perspective by Youle) present evidence that the default state of Bax and Bak would lead to cell death. Cells lacking the direct activators of Bax and Bak still undergo apoptosis in response to overexpression of upstream components of the cell death pathway.

S. N. Willis, J. I. Fletcher, T. Kaufmann, M. F. van Delft, L. Chen, P. E. Czabotar, H. Ierino, E. F. Lee, W. D. Fairlie, P. Bouillet, A. Strasser, R. M. Kluck, J. M. Adams, D. C. S. Huang, Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315, 856-859 (2007). [Abstract] [Full Text]

R. J. Youle, Cellular demolition and the rules of engagement. Science 315, 776-777 (2007). [Summary] [Full Text]