BID, A BCL2 INTERACTING PROTEIN, MEDIATES CYTOCHROME-C RELEASE FROM MITOCHONDRIA IN RESPONSE TO ACTIVATION OF CELL-SURFACE DEATH RECEPTORS

We report here the purification of a cytosolic protein that induces cy tochrome c release from mitochondria in response to caspase-8, the api cal caspase activated by cell surface death receptors such as Fas and TNF. Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bar. C aspase-8 cleaves Bid, and the COOH-terminal part translocates to mitoc hondria where it triggers cytochrome c release. Immunodepletion of Bid from cell extracts eliminated the cytochrome c releasing activity. Th e cytochrome c releasing activity of Bid was antagonized by Bcl2. A mu tation at the BH3 domain diminished its cytochrome c releasing activit y. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria.