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Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death

Science  27 Apr 2001:
Vol. 292, Issue 5517, pp. 727-730
DOI: 10.1126/science.1059108

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Abstract

Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a “BH3-domain–only” BCL-2 family member, triggers the homooligomerization of “multidomain” conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax andBak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a “multidomain” proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: craig{at}mail.med.upem.edu; stanley_korsmeyer{at}dfci.harvard.edu

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