Bid Induces the Oligomerization and Insertion of Bax into the Outer Mitochondrial Membrane

doi:10.1128/MCB.20.3.929-935.2000

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Molecular and Cellular Biology, February 2000, p. 929-935, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Bid Induces the Oligomerization and Insertion of Bax into the Outer Mitochondrial Membrane

Robert Eskes, Solange Desagher, Bruno Antonsson, and Jean-Claude Martinou^*

Serono Pharmaceutical Research Institute, Ares Serono International S.A., CH-1228 Plan-les Ouates, Geneva, Switzerland

Received 21 June 1999/Returned for modification 9 August 1999/Accepted 25 October 1999

In many types of apoptosis, the proapoptotic protein Bax undergoes a change in conformation at the level of the mitochondria.This event always precedes the release of mitochondrial cytochromec, which, in the cytosol, activates caspases through binding toApaf-1. The mechanisms by which Bax triggers cytochrome c releaseare unknown. Here we show that following binding to the BH3-domain-onlyproapoptotic protein Bid, Bax oligomerizes and then integratesin the outer mitochondrial membrane, where it triggers cytochromec release. Bax mitochondrial membrane insertion triggered by Bidmay represent a key step in pathways leading toapoptosis.

^* Corresponding author. Mailing address: Serono Pharmaceutical Research Institute, Ares Serono International S.A., 14 Chemindes Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland. Phone:41-22-706-9822. Fax: 41-22-794-69-65. E-mail: Jean-Claude.Martinou{at}Serono.com.

Present address: J. W. G.-University Frankfurt am Main, ZIM $---$ Med Klinik III $---$ Molekulare Hämatologie, D-60596 FrankfurtGermany.

Molecular and Cellular Biology, February 2000, p. 929-935, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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