Crossed TRAILs

Apoptosis appeared to be a tale of many proteins but two distinct pathways. The extrinsic pathway leads from cell receptors to caspase 8, whereas the intrinsic pathway leads from cellular stresses (such as DNA damage) via mitochondria to caspase 9. But then came evidence that caspase 8 could help release cytochrome c from mitochondria. In new work, Xiangwei Wu and colleagues (Baylor College of Medicine, Houston, TX) have added another link between the two pathways, and indicated that Smac, not cyt c, may be the critical protein to be released from mitochondria.Wu began his study by looking at the death ligand TRAIL. Apoptosis triggered by TRAIL was blocked by the antiapoptotic Bcl-xL and required the proapoptotic Bax—two proteins that act via mitochondria. Without Bax, TRAIL still activated caspase 8 but did not trigger...