Preservation of Mitochondrial Structure and Function after Bid- or Bax-Mediated Cytochrome c Release

Preservation of Mitochondrial Structure and Function after Bid- or Bax-Mediated Cytochrome c Release Proapoptotic members of the Bcl-2 protein family, including Bid and Bax, can activate apoptosis by directly interacting with mitochondria to cause cytochrome c translocation from the intermembrane space into the cytoplasm, thereby triggering Apaf-1–mediated caspase activation. Under some circumstances, when caspase activation is blocked, cells can recover from cytochrome c translocation; this suggests that apoptotic mitochondria may not always suffer catastrophic damage arising from the process of cytochrome c release. We now show that recombinant Bid and Bax cause complete cytochrome c loss from isolated mitochondria in vitro, but preserve the ultrastructure and protein import function of mitochondria, which depend on inner membrane polarization. We also demonstrate that, if caspases are inhibited, mitochondrial protein import function is retained in UV-irradiated or staurosporine-treated cells, despite the complete translocation of cytochrome c . Thus, Bid and Bax act only on the outer membrane, and lesions in the inner membrane occurring during apoptosis are shown to be secondary caspase-dependent events. apoptosis mitochondria membrane potential protein import electron microscopy Footnotes Abbreviations used in this paper: ΔΨ m , mitochondrial membrane potential; MIB, mitochondrial isolation buffer; PT, permeability transition. Submitted: 17 March 2000 Revision requested 8 June 2000 Accepted: 13 July 2000 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

Preservation of Mitochondrial Structure and Function after Bid- or Bax-Mediated Cytochrome c Release

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Publisher
Rockefeller University Press
Copyright
© 2000 The Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.150.5.1027
Publisher site
See Article on Publisher Site

Abstract

Proapoptotic members of the Bcl-2 protein family, including Bid and Bax, can activate apoptosis by directly interacting with mitochondria to cause cytochrome c translocation from the intermembrane space into the cytoplasm, thereby triggering Apaf-1–mediated caspase activation. Under some circumstances, when caspase activation is blocked, cells can recover from cytochrome c translocation; this suggests that apoptotic mitochondria may not always suffer catastrophic damage arising from the process of cytochrome c release. We now show that recombinant Bid and Bax cause complete cytochrome c loss from isolated mitochondria in vitro, but preserve the ultrastructure and protein import function of mitochondria, which depend on inner membrane polarization. We also demonstrate that, if caspases are inhibited, mitochondrial protein import function is retained in UV-irradiated or staurosporine-treated cells, despite the complete translocation of cytochrome c . Thus, Bid and Bax act only on the outer membrane, and lesions in the inner membrane occurring during apoptosis are shown to be secondary caspase-dependent events. apoptosis mitochondria membrane potential protein import electron microscopy Footnotes Abbreviations used in this paper: ΔΨ m , mitochondrial membrane potential; MIB, mitochondrial isolation buffer; PT, permeability transition. Submitted: 17 March 2000 Revision requested 8 June 2000 Accepted: 13 July 2000

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Sep 4, 2000

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