Modulating Death and Stress

Science's STKE  02 May 2006:
Vol. 2006, Issue 333, pp. tw148
DOI: 10.1126/stke.3332006tw148

The proteins BAX and BAK are key regulators of apoptosis, and one or the other has to be engaged to activate mitochondrial effects that lead to cell death. Studying cells from knockout mice lacking BAX and BAK, Hetz et al. discovered another role for these proteins by which cells adapt to stresses that involve the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The unfolded protein response's protective effects were disrupted in the BAX-BAK double-knockout cells, apparently through the loss of direct interaction of BAX or BAK with the sensor for ER stress. Thus, BAX and BAK may act at multiple organelles to coordinate cellular responses to stress with the control of cell death.

C. Hetz, P. Bernasconi, J. Fisher, A.-H. Lee, M. C. Bassik, B. Antonsson, G. S. Brandt, N. N. Iwakoshi, A. Schinzel, L. H. Glimcher, S. J. Korsmeyer, Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1α. Science 312, 572-576 (2006). [Abstract] [Full Text]