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PMID: 17453159 Published · ppublish English Journal Article Review

Embedded together: the life and death consequences of interaction of the Bcl-2 family with membranes.

Apoptosis : an international journal on programmed cell death ·Vol. 12 ·No. 5 ·2007-05-00 ·Pages 897-911

Leber B, Lin J, Andrews DW

Abstract

Permeabilization of the outer mitochondrial membrane is the point of no return in most programmed cell deaths. This critical step is mainly regulated by the various protein-protein and protein-membrane interactions of the Bcl-2 family proteins. The two main models for regulation of mitochondrial outer membrane permeabilization, direct activation and displacement do not account for all of the experimental data and both largely neglect the importance of the membrane. We propose the embedding together model to emphasize the critical importance of Bcl-2 family protein interactions with and within membranes. The embedding together model proposes that both pro- and anti-apoptotic Bcl-2 family proteins engage in similar dynamic interactions that are governed by membrane dependent conformational changes and culminate in either aborted or productive membrane permeabilization depending on the final oligomeric state of pro-apoptotic Bax and/or Bak.

MeSH Terms
Animals Apoptosis/physiology Humans Intracellular Membranes/metabolism Membrane Potentials/physiology Membrane Proteins/metabolism Mitochondria/metabolism Mitochondrial Proteins/metabolism Models, Theoretical Permeability Proto-Oncogene Proteins c-bcl-2/metabolism bcl-2 Homologous Antagonist-Killer Protein/metabolism bcl-2-Associated X Protein/metabolism
Chemicals
Membrane Proteins Mitochondrial Proteins Proto-Oncogene Proteins c-bcl-2 bcl-2 Homologous Antagonist-Killer Protein bcl-2-Associated X Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Leber Brian
Departments of Biochemistry and Biomedical Sciences and Medicine, McMaster University, Hamilton, Ontario, Canada.
Lin Jialing
Andrews David W
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Article Info
Journal
Apoptosis : an international journal on programmed cell death
Abbr.
Apoptosis
ISSN
1360-8185
DOI
10.1007/s10495-007-0746-4
Published
2007-05-00
Pages
897-911
Language
English
Region
Netherlands
NLM ID
9712129
PMCID
PMC2868339
Subset
IM
Grants
NIGMS NIH HHS · R01 GM062964 · United States
NIGMS NIH HHS · R01 GM062964-06A1 · United States
External Links
PubMed source DOI: 10.1007/s10495-007-0746-4 PMC Full Text View journal details
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