BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane

Schug, Z.T., Gonzalvez, F., Houtkooper, R.H., Vaz, F.M. and Gottlieb, E. (2011) BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane. Cell Death and Differentiation, 18(3), pp. 538-548. (doi: 10.1038/cdd.2010.135)

Abstract

Caspase-8 stably inserts into the mitochondrial outer membrane during extrinsic apoptosis. Inhibition of caspase-8 enrichment on the mitochondria impairs caspase-8 activation and prevents apoptosis. However, the function of active caspase-8 on the mitochondrial membrane remains unknown. In this study, we have identified a native complex containing caspase-8 and BID on the mitochondrial membrane, and showed that death receptor activation by Fas or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced the cleavage of BID (tBID formation) within this complex. tBID then shifted to separate mitochondria-associated complexes that contained other BCL-2 family members, such as BAK and BCL-XL. We report that cells stabilize active caspase-8 on the mitochondria in order to specifically target mitochondria-associated BID, and that BID cleavage on the mitochondria is essential for caspase-8-induced cytochrome c release. Our findings indicate that during extrinsic apoptosis, caspase-8 can specifically target BID where it is mostly needed, on the surface of mitochondria.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gonzalvez, Mr Francois and Gottlieb, Professor Eyal and Schug, Dr Zachary
• Authors: Schug, Z.T., Gonzalvez, F., Houtkooper, R.H., Vaz, F.M., and Gottlieb, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Death and Differentiation
• ISSN: 1350-9047