Managing Mitochondrial Mortality Messages

Abstract

The proteins BAK and BAX are proapoptotic members of the "BH3-domain-only" family of proteins (so-called because they share with the BCL-2 family of proteins only the third of four BCL-2-homology domains). Wei et al. provide evidence that BAK and BAX are essential gatekeepers for apoptotic signals that act through the mitochondria. Signals from death receptors on the cell surface cause activation of tBID (another BH3-domain-only family member), which leads to release of cytochrome c from mitochondria and subsequent cell death. Cells that lacked BAK or BAX alone were still sensitive to tBID, but cells deficient in both proteins did not undergo tBID-induced apoptosis. A broad range of signals from the plasma membrane, nucleus, and endoplasmic reticulum required the presence of BAK or BAX and thus appear to promote cell death through signals that converge at the mitochondria. M. C. Wei, W.-X. Zong, E. H.-Y. Cheng, T. Lindsten, V. Panoutsakopoulou, A. J. Ross, K. A. Roth, G. R. MacGregor, C. B. Thompson, S. J. Korsmeyer, Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 292 , 727-730 (2001). [Abstract] [Full Text]