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Updated: Jun 6, 2026
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Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane
Z T Schug1, F Gonzalvez, R H Houtkooper
1Laboratory of Apoptosis and Tumour Metabolism, Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
Cell Death and Differentiation
|November 13, 2010
Summary
Active caspase-8 targets BID on mitochondria during extrinsic apoptosis, initiating cytochrome c release and cell death. This mitochondrial targeting is crucial for apoptosis execution.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Caspase-8 localizes to the mitochondrial outer membrane during extrinsic apoptosis.
- Mitochondrial caspase-8 enrichment is vital for its activation and subsequent apoptosis.
- The precise function of active caspase-8 at the mitochondria remains unclear.
Purpose of the Study:
- To elucidate the role of active caspase-8 on the mitochondrial membrane during extrinsic apoptosis.
- To identify interacting partners of caspase-8 at the mitochondria.
- To determine the necessity of mitochondrial caspase-8 activity for apoptosis.
Main Methods:
- Mitochondrial isolation and biochemical fractionation.
- Co-immunoprecipitation assays to identify protein complexes.
- Western blotting to detect protein cleavage and localization.
- Analysis of apoptosis markers, including cytochrome c release.
Main Results:
- A native complex of caspase-8 and BID was identified on the mitochondrial membrane.
- Death receptor activation (Fas, TRAIL) induced BID cleavage (tBID formation) within this mitochondrial complex.
- tBID translocated to other mitochondria-associated complexes containing BCL-2 family members (BAK, BCL-X(L)).
- Mitochondrial caspase-8 specifically targets BID on the mitochondrial surface, which is essential for cytochrome c release.
Conclusions:
- Caspase-8 stabilizes on mitochondria to specifically cleave BID.
- BID cleavage on mitochondria is a critical step for caspase-8-mediated cytochrome c release and apoptosis.
- This study reveals a targeted mechanism for caspase-8 action at the mitochondria during extrinsic apoptosis.
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