Unmixing Apoptotic Signals

Science's STKE  08 Apr 2003:
Vol. 2003, Issue 177, pp. tw141-TW141
DOI: 10.1126/stke.2003.177.tw141

The Bax and Bak proteins have been said to provide a "mitochondrial gateway" to apoptosis or cell death, because stimuli that cause death through effects on mitochondria require the action of one or the other of these proteins at the outer mitochondrial membrane. Scorrano et al. (see the Perspective by Demaurex and Distelhorst) show that these proteins have a similar role as an essential gateway through which apoptotic signals affect Ca2+ release from the endoplasmic reticulum (ER) and consequent changes in concentrations of Ca2+ in the mitochondria that lead to cell death signals. Cells lacking both Bax and Bak had decreased concentrations of Ca2+ in the ER. The authors selectively restored Ca2+ regulation in the mitochondria or the ER and distinguished three different classes of apoptotic stimuli. Stimuli like arachidonic acid or C2-ceramide require action of Bax or Bak at the ER. The so-called BH3-only apoptotic proteins require only restoration of Bax or Bak at the mitochondria to cause death. Finally, intrinsic cellular stress signals require Bax and Bak function in both organelles.

L. Scorrano, S. A. Oakes, J. T. Opferman, E. H. Cheng, M. D. Sorcinelli, T. Pozzan, S. J. Korsmeyer, BAX and BAK regulation of endoplasmic reticulum Ca2+: A control point for apoptosis. Science 300, 135-139 (2003). [Abstract] [Full Text]

N. Demaurex, C. Distelhorst, Apoptosis--the calcium connection. Science 300, 65-67 (2003). [Summary] [Full Text]