The study investigates the mechanisms by which the proapoptotic protein Bax triggers cytochrome c release from mitochondria, a key step in apoptosis. Bax undergoes a conformational change when bound to the BH3-domain-only protein Bid, which then facilitates Bax's oligomerization and insertion into the outer mitochondrial membrane. This insertion is followed by cytochrome c release, which is highly dependent on magnesium ions. The study also shows that Bcl-xL and Bcl-2 can inhibit Bid-induced Bax oligomerization and insertion, suggesting that these antiapoptotic proteins counteract the Bid-induced conformational change of Bax. The findings provide insights into the molecular mechanisms underlying the activation of apoptosis and highlight the importance of Bax's localization in the outer mitochondrial membrane for its apoptotic function.The study investigates the mechanisms by which the proapoptotic protein Bax triggers cytochrome c release from mitochondria, a key step in apoptosis. Bax undergoes a conformational change when bound to the BH3-domain-only protein Bid, which then facilitates Bax's oligomerization and insertion into the outer mitochondrial membrane. This insertion is followed by cytochrome c release, which is highly dependent on magnesium ions. The study also shows that Bcl-xL and Bcl-2 can inhibit Bid-induced Bax oligomerization and insertion, suggesting that these antiapoptotic proteins counteract the Bid-induced conformational change of Bax. The findings provide insights into the molecular mechanisms underlying the activation of apoptosis and highlight the importance of Bax's localization in the outer mitochondrial membrane for its apoptotic function.