Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-X(L) prevents this release but not tumor necrosis factor-R1/Fas death

Atan Gross, Xiao Ming Yin, Kun Wang, Michael C. Wei, Jennifer Jockel, Curt Milliman, Hediye Erdjument-Bromage, Paul Tempst, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

891 Scopus citations

Abstract

'BH3 domain only' members of the BCL-2 family including the pro- apoptotic molecule BID represent candidates to connect with proximal signal transduction. Tumor necrosis factor α (TNFα) treatment induced a caspase- mediated cleavage of cytosolic, inactive p22 BID at internal Asp sites to yield a major p15 and minor p13 and p11 fragments. p15 BID translocates to mitochondria as an integral membrane protein. p15 BID within cytosol targeted normal mitochondria and released cytochrome c. Immunodepletion of p15 BID prevents cytochrome c release. In vivo, anti-Fas Ab results in the appearance of p15 BID in the cytosol of hepatocytes which translocates to mitochondria where it releases cytochrome c. Addition of activated caspase-8 to normal cytosol generates p15 BID which is also required in this system for release of cytochrome c. In the presence of BCL-X(L)/BCL-2, TNFα still induced BID cleavage and p15 BID became an integral mitochondrial membrane protein. However, BCL-X(L)/BCL-2 prevented the release of cytochrome c, yet other aspects of mitochondrial dysfunction still transpired and cells died nonetheless. Thus, while BID appears to be required for the release of cytochrome c in the TNF death pathway, the release of cytochrome e may not be required for cell death.

Original languageEnglish (US)
Pages (from-to)1156-1163
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number2
DOIs
StatePublished - Jan 8 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-X(L) prevents this release but not tumor necrosis factor-R1/Fas death'. Together they form a unique fingerprint.

  • Cite this

    Gross, A., Yin, X. M., Wang, K., Wei, M. C., Jockel, J., Milliman, C., Erdjument-Bromage, H., Tempst, P., & Korsmeyer, S. J. (1999). Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-X(L) prevents this release but not tumor necrosis factor-R1/Fas death. Journal of Biological Chemistry, 274(2), 1156-1163. https://doi.org/10.1074/jbc.274.2.1156