Abstract
In the absence of an apoptotic signal, BAX adopts a conformation that constrains the protein from integrating into mitochondrial membranes. Here, we show that caspases, including caspase-8, can initiate BAX insertion into mitochondria in vivo and in vitro. The cleavage product of caspase-8, tBID, induced insertion of BAX into mitochondria in vivo, and reconstitution in vitro showed that tBID, either directly or indirectly, relieved inhibition of the BAX transmembrane signal-anchor by the NH2- terminal domain, resulting in integration of BAX into mitochondrial membrane. In contrast to these findings, however, Bid-null mouse embryo fibroblasts supported Bax insertion into mitochondria in response to death signaling by either TNFα or E1A, despite the fact that cytochrome c release from the organelle was inhibited. We conclude, therefore, that a parallel Bid-independent pathway exists in these cells for mitochondrial insertion of Bax and that, in the absence of Bid, cytochrome c release can be uncoupled from Bax membrane insertion.
Original language | English (US) |
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Pages (from-to) | 1101-1108 |
Number of pages | 8 |
Journal | Cell Death and Differentiation |
Volume | 7 |
Issue number | 11 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Apoptosis
- BAX
- BID
- E1A
- Fas
- Mitochondria
- TNF
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology