Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Membrane Proteins
  • Mitochondria
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2

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 and Bak, 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.

publication date

  • April 27, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3049805

Digital Object Identifier (DOI)

  • 10.1126/science.1059108

PubMed ID

  • 11326099

Additional Document Info

start page

  • 727

end page

  • 30

volume

  • 292

number

  • 5517