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PMID: 10973993 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Preservation of mitochondrial structure and function after Bid- or Bax-mediated cytochrome c release.

The Journal of cell biology ·Vol. 150 ·No. 5 ·2000-09-04 ·Pages 1027-36

von Ahsen O, Renken C, Perkins G, Kluck RM, Bossy-Wetzel E, Newmeyer DD

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.

MeSH Terms
Animals Apoptosis/drug effects,physiology,radiation effects BH3 Interacting Domain Death Agonist Protein Carrier Proteins/metabolism Cyclosporine/pharmacology Cytochrome c Group/metabolism Female HL-60 Cells HeLa Cells Humans Intracellular Membranes/drug effects,physiology,radiation effects,ultrastructure Mitochondria/physiology,ultrastructure Oocytes/physiology,ultrastructure Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-2 Recombinant Proteins/metabolism Staurosporine/pharmacology Ultraviolet Rays Xenopus laevis bcl-2-Associated X Protein
Chemicals
BAX protein, human BH3 Interacting Domain Death Agonist Protein BID protein, human Carrier Proteins Cytochrome c Group Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Recombinant Proteins bcl-2-Associated X Protein Cyclosporine Staurosporine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
von Ahsen O
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Renken C
Perkins G
Kluck R M
Bossy-Wetzel E
Newmeyer D D
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.150.5.1027
Published
2000-09-04
Pages
1027-36
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2175243
Subset
IM
Grants
NIGMS NIH HHS · R25-GM58906 · United States
NIGMS NIH HHS · GM50284 · United States
NIA NIH HHS · AG00252-02 · United States
External Links
PubMed source DOI: 10.1083/jcb.150.5.1027 PMC Full Text View journal details
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