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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,dagger 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 cytochrome c, which, in the cytosol, activates caspases through binding to Apaf-1. The mechanisms by which Bax triggers cytochrome c release are unknown. Here we show that following binding to the BH3-domain-only proapoptotic protein Bid, Bax oligomerizes and then integrates in the outer mitochondrial membrane, where it triggers cytochrome c release. Bax mitochondrial membrane insertion triggered by Bid may represent a key step in pathways leading to apoptosis.

* Corresponding author. Mailing address: Serono Pharmaceutical Research Institute, Ares Serono International S.A., 14 Chemin des 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.

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

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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