BID-dependent and BID-independent pathways for BAX insertion into mitochondria

S. C. Ruffolo, D. G. Breckenridge, M. Nguyen, I. S. Goping, A. Gross, S. J. Korsmeyer, Honglin Li, J. Yuan, G. C. Shore

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

In the absence of an apoptotic signal, BAX adopts a conformation that constrains the protein from integrating into mitochondrial membranes. Here, we show that caspases, including caspase-8, can initiate BAX insertion into mitochondria in vivo and in vitro. The cleavage product of caspase-8, tBID, induced insertion of BAX into mitochondria in vivo, and reconstitution in vitro showed that tBID, either directly or indirectly, relieved inhibition of the BAX transmembrane signal-anchor by the NH2- terminal domain, resulting in integration of BAX into mitochondrial membrane. In contrast to these findings, however, Bid-null mouse embryo fibroblasts supported Bax insertion into mitochondria in response to death signaling by either TNFα or E1A, despite the fact that cytochrome c release from the organelle was inhibited. We conclude, therefore, that a parallel Bid-independent pathway exists in these cells for mitochondrial insertion of Bax and that, in the absence of Bid, cytochrome c release can be uncoupled from Bax membrane insertion.

Original languageEnglish (US)
Pages (from-to)1101-1108
Number of pages8
JournalCell Death and Differentiation
Volume7
Issue number11
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Apoptosis
  • BAX
  • BID
  • E1A
  • Fas
  • Mitochondria
  • TNF

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Ruffolo, S. C., Breckenridge, D. G., Nguyen, M., Goping, I. S., Gross, A., Korsmeyer, S. J., Li, H., Yuan, J., & Shore, G. C. (2000). BID-dependent and BID-independent pathways for BAX insertion into mitochondria. Cell Death and Differentiation, 7(11), 1101-1108. https://doi.org/10.1038/sj.cdd.4400739