Caspase Cleaved BID Targets Mitochondria and Is Required for Cytochrome c Release, while BCL-XL Prevents This Release but Not Tumor Necrosis Factor-R1/Fas Death
Open accessAbstract
"BH3 domain only" members of the BCL-2 family including the pro-apoptotic molecule BID represent candidates to connect with proximal signal transduction. Tumor necrosis factor alpha (TNFalpha) treatment induced a caspase-mediated cleavage of cytosolic, inactive p22 BID at internal Asp sites to yield a major p15 and minor p13 and p11 fragments. p15 BID translocates to mitochondria as an integral membrane protein. p15 BID within cytosol targeted normal mitochondria and released cytochrome c. Immunodepletion of p15 BID prevents cytochrome c release. In vivo, anti-Fas Ab results in the appearance of p15 BID in the cytosol of hepatocytes which translocates to mitochondria where it releases cytochrome c. Addition of activated caspase-8 to normal cytosol generates p15 BID which is also required in this system for release of cytochrome c. In the presence of BCL-XL/BCL-2, TNFalpha still induced BID cleavage and p15 BID became an integral mitochondrial membrane protein. However, BCL-XL/BCL-2 prevented the release of cytochrome c, yet other aspects of mitochondrial dysfunction still transpired and cells died nonetheless. Thus, while BID appears to be required for the release of cytochrome c in the TNF death pathway, the release of cytochrome c may not be required for cell death.
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Cleavage of BID by CASP8 leads to generation of tBID, which translocates to OMM.
“This leads to the generation of a truncated form of BID (tBID), which translocates to the OMM [313, 314]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [313]
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- Authors
- Gross, A., Yin, X.-M., Wang, K., Wei, M. C., Jockel, J., Milliman, C., Erdjument-Bromage, H., Tempst, P., & Korsmeyer, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Korsmeyer, Stanley J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 274
- Issue
- 2
- Pages
- 1156-1163
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2075477970
- Cited by
- 1,045
- References
- 60
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 4 · 2023: 7 · 2022: 15 · 2021: 37 · 2020: 9 · 2019: 10 · 2018: 18 · 2017: 15 · 2016: 12 · 2015: 27 · 2014: 17 · 2013: 31 · 2012: 27
- FWCI
- 37.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- 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 cleavage, cytochrome c release, mitochondria, Bcl-xL, Bcl-2, TNF-α, TNFR1, BH3-only proteins, apoptosis, caspase-8, hepatocytes, mitochondrial membrane proteins
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Cycloheximide, Cytochrome c Group, Cytosol, Hydrolysis, Mitochondria, Molecular Sequence Data, Tumor Necrosis Factor-alpha, Antigens, CD, Apoptosis, Receptors, Tumor Necrosis Factor, fas Receptor, Proto-Oncogene Proteins c-bcl-2, Caspases, Receptors, Tumor Necrosis Factor, Type I, bcl-X Protein, BH3 Interacting Domain Death Agonist Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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