Bc1-2 family members and functional electron transport chain regulate oxygen deprivation-induced cell death

D. S. McClintock, M. T. Santore, V. Y. Lee, J. Brunelle, G. R. Scott Budinger, W. X. Zong, C. B. Thompson, N. Hay, N. S. Chandel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

The mechanisms underlying cell death during oxygen deprivation are unknown. We report here a model for oxygen deprivation-induced apoptosis. The death observed during oxygen deprivation involves a decrease in the mitochondrial membrane potential, followed by the release of cytochrome c and the activation of caspase-9. Bc1-XL prevented oxygen deprivation-induced cell death by inhibiting the release of cytochrome c and caspase-9 activation. The ability of Bc1-XL to prevent cell death was dependent on allowing the import of glycolytic ATP into the mitochondria to generate an inner mitochondrial membrane potential through the F1F0-ATP synthase. In contrast, although activated Akt has been shown to inhibit apoptosis induced by a variety of apoptotic stimuli, it did not prevent cell death during oxygen deprivation. In addition to Bc1-XL, cells devoid of mitochondrial DNA (po cells) that lack a functional electron transport chain were resistant to oxygen deprivation. Further, murine embryonic fibroblasts from bax-/- bak-/- mice did not die in response to oxygen deprivation. These data suggest that when subjected to oxygen deprivation, cells die as a result of an inability to maintain a mitochondrial membrane potential through the import of glycolytic ATP. Proapoptotic Bc1-2 family members and a functional electron transport chain are required to initiate cell death in response to oxygen deprivation.

Original languageEnglish (US)
Pages (from-to)94-104
Number of pages11
JournalMolecular and cellular biology
Volume22
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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