Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis
Open accessAbstract
We report here that BID, a BH3 domain-containing proapoptotic Bcl2 family member, is a specific proximal substrate of Casp8 in the Fas apoptotic signaling pathway. While full-length BID is localized in cytosol, truncated BID (tBID) translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria. tBID induces first the clustering of mitochondria around the nuclei and release of cytochrome c independent of caspase activity, and then the loss of mitochondrial membrane potential, cell shrinkage, and nuclear condensation in a caspase-dependent fashion. Coexpression of BclxL inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8.
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In type II cells, extrinsic apoptosis requires proteolytic cleavage of BID by CASP8.
“extrinsic apoptosis requires the proteolytic cleavage of BID by CASP8 [70, 311, 312].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [312]
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- Authors
- Li, H., Zhu, H., Xu, C.-J., & Yuan, J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Yuan, Junying
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 94
- Issue
- 4
- Pages
- 491-501
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2062853648
- Cited by
- 4,445
- References
- 0
- Citations by year
- 2026: 42 · 2025: 64 · 2024: 55 · 2023: 70 · 2022: 56 · 2021: 116 · 2020: 69 · 2019: 88 · 2018: 91 · 2017: 111 · 2016: 123 · 2015: 115 · 2014: 137 · 2013: 159 · 2012: 183
- FWCI
- 80.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Bid, caspase-8, mitochondrial damage, truncated Bid, mitochondrial translocation, cytochrome c release, mitochondrial membrane potential, Bcl-xL, Bcl-2 family proteins, apoptosis, BH3 domain
- MeSH terms
- Animals, Carrier Proteins, Cell Nucleus, Cysteine Endopeptidases, Cytochrome c Group, Humans, Mitochondria, Peptide Fragments, Substrate Specificity, Tumor Necrosis Factor-alpha, Signal Transduction, Apoptosis, fas Receptor, Proto-Oncogene Proteins c-bcl-2, Caspases, Cell Size, bcl-X Protein, BH3 Interacting Domain Death Agonist Protein, Mice, Caspase 8, Caspase 9
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