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Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c.

Publication ,  Journal Article
Kuwana, T; Smith, JJ; Muzio, M; Dixit, V; Newmeyer, DD; Kornbluth, S
Published in: The Journal of biological chemistry
June 1998

Apoptosis often involves the release of cytochrome c from mitochondria, leading to caspase activation. However, in apoptosis mediated by CD95 (Fas/APO-1), caspase-8 (FLICE/MACH/Mch5) is immediately activated and, in principle, could process other caspases directly. To investigate whether caspase-8 could also act through mitochondria, we added active caspase-8 to a Xenopus cell-free system requiring these organelles. Caspase-8 rapidly promoted the apoptotic program, culminating in fragmentation of chromatin and the nuclear membrane. In extracts devoid of mitochondria, caspase-8 produced DNA degradation, but left nuclear membranes intact. Thus, mitochondria were required for complete engagement of the apoptotic machinery. In the absence of mitochondria, high concentrations of caspase-8 were required to activate downstream caspases. However, when mitochondria were present, the effects of low concentrations of caspase-8 were vastly amplified through cytochrome c-dependent caspase activation. Caspase-8 promoted cytochrome c release indirectly, by cleaving at least one cytosolic substrate. Bcl-2 blocked apoptosis only at the lowest caspase-8 concentrations, potentially explaining why CD95-induced apoptosis can often evade inhibition by Bcl-2.

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Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

June 1998

Volume

273

Issue

26

Start / End Page

16589 / 16594

Related Subject Headings

  • Xenopus
  • Proto-Oncogene Proteins c-bcl-2
  • Peptide Hydrolases
  • Mitochondria
  • Cytochrome c Group
  • Cysteine Proteinase Inhibitors
  • Cysteine Endopeptidases
  • Cell-Free System
  • Caspases
  • Caspase 9
 

Citation

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Kuwana, T., Smith, J. J., Muzio, M., Dixit, V., Newmeyer, D. D., & Kornbluth, S. (1998). Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. The Journal of Biological Chemistry, 273(26), 16589–16594. https://doi.org/10.1074/jbc.273.26.16589
Kuwana, T., J. J. Smith, M. Muzio, V. Dixit, D. D. Newmeyer, and S. Kornbluth. “Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c.The Journal of Biological Chemistry 273, no. 26 (June 1998): 16589–94. https://doi.org/10.1074/jbc.273.26.16589.
Kuwana T, Smith JJ, Muzio M, Dixit V, Newmeyer DD, Kornbluth S. Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. The Journal of biological chemistry. 1998 Jun;273(26):16589–94.
Kuwana, T., et al. “Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c.The Journal of Biological Chemistry, vol. 273, no. 26, June 1998, pp. 16589–94. Epmc, doi:10.1074/jbc.273.26.16589.
Kuwana T, Smith JJ, Muzio M, Dixit V, Newmeyer DD, Kornbluth S. Apoptosis induction by caspase-8 is amplified through the mitochondrial release of cytochrome c. The Journal of biological chemistry. 1998 Jun;273(26):16589–16594.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

June 1998

Volume

273

Issue

26

Start / End Page

16589 / 16594

Related Subject Headings

  • Xenopus
  • Proto-Oncogene Proteins c-bcl-2
  • Peptide Hydrolases
  • Mitochondria
  • Cytochrome c Group
  • Cysteine Proteinase Inhibitors
  • Cysteine Endopeptidases
  • Cell-Free System
  • Caspases
  • Caspase 9