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Springer, Apoptosis, 5(12), p. 897-911, 2007

DOI: 10.1007/s10495-007-0746-4

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Embedded Together: The Life and Death Consequences of Interaction of the Bcl-2 Family with Membranes

Journal article published in 2007 by Brian Leber, Jialing Lin, David W. Andrews ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.