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

Abstract

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 cytochromec release. Bax mitochondrial membrane insertion triggered by Bid may represent a key step in pathways leading to apoptosis.

ACKNOWLEDGMENTS

We thank S. Arkinstall and K. Maundrell for critical reading of the manuscript, C. Herbert for artwork, and T. Wells for encouraging support.

Part of this work was also supported by grants from the European Community (Biotech grant BIO4CT96 0774 to J.-C. Martinou).