The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Open accessAbstract
A cell-free system based on cytosols of normally growing cells is established that reproduces aspects of the apoptotic program in vitro. The apoptotic program is initiated by addition of dATP. Fractionation of cytosol yielded a 15 kDa protein that is required for in vitro apoptosis. The absorption spectrum and protein sequence revealed that this protein is cytochrome c. Elimination of cytochrome c from cytosol by immunodepletion, or inclusion of sucrose to stabilize mitochondria during cytosol preparation, diminished the apoptotic activity. Adding back cytochrome c to the cytochrome c-depleted extracts restored their apoptotic activity. Cells undergoing apoptosis in vivo showed increased release of cytochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“MOMP directly promotes the cytosolic release of apoptogenic factors that normally reside in the mitochondrial intermembrane space [40, 44, 156]. These mitochondrial proteins include (but are not limited to) cytochrome c, somatic (CYCS), which usually operates as an electron shuttle in the mitochondrial respiratory chain [157–160], and diablo IAP-binding mitochondrial protein (DIABLO; also known as”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [158]
In the citing paper
“If the pathological threshold is crossed, the electron transfer chain is disrupted, reactive oxygen species accumulate, the permeability transition pore opens, the outer mitochondrial membrane ruptures, cytochrome c is released, and an apoptotic cell death program is activated [86,109].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [86]
In the citing paper
“A substantial quantity of cytochrome c and cytochrome c oxidase supports the high bioenergetic needs of PV-INs [81,85], but comes at a price as cytochrome c is also central to the induction of apoptosis [86].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [86]
In the citing paper
“A key event in this process involves mitochondrial outer membrane permeabilization (MOMP) and the remodeling of mitochondrial membranes, permitting the release of apoptogenic factors such as cytochrome c (Liu et al., 1996) and apoptosis-inducing factor (AIF) (Susin et al., 1999) from the intermembrane space into the cytosol (Kroemer et al., 2007).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Liu et al., 1996
Citations
Cites
Cell Death: The Significance of Apoptosis
Wyllie, A. H., Kerr, J. F. R., & Currie, A. R. (1980) · International review of cytology · doi:10.1016/s0074-7696(08)62312-8 · Cited by 7,151
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
Wyllie, A. H. (1980) · Nature · doi:10.1038/284555a0 · Cited by 4,499
Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
Nicholson, D. W., Ali, A., Thornberry, N. A., Vaillancourt, J. P., Ding, C. K., Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M., Lazebnik, Y. A., et al. (1995) · Nature · doi:10.1038/376037a0 · Cited by 3,980
Bcl-2 functions in an antioxidant pathway to prevent apoptosis
Hockenbery, D. M., Oltvai, Z. N., Yin, X., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)80066-n · Cited by 3,402
A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Molineaux, S. M., Weidner, J. R., Aunins, J. G., et al. (1992) · Nature · doi:10.1038/356768a0 · Cited by 2,613
Ji, Y. (1993) · Cell · doi:10.1016/0092-8674(93)90485-9 · Cited by 2,497
Mechanisms and Genes of Cellular Suicide
Steller, H. (1995) · Science · doi:10.1126/science.7878463 · Cited by 2,469
Tewari, M., Quan, L. T., O’Rourke, K. M., Desnoyers, S., Zeng, Z., Beidler, D. R., Poirier, G. G., Salvesen, G. S., & Dixit, V. M. (1995) · Cell · doi:10.1016/0092-8674(95)90541-3 · Cited by 2,367
Bcl-2 and the regulation of programmed cell death
Reed, J. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.124.1.1 · Cited by 2,287
Kaufmann, S. H., Desnoyers, S., Ottaviano, Y. L., Davidson, N. E., & Poirier, G. G. (1993) · PubMed · Cited by 1,889
Life, death, and the pursuit of apoptosis.Preprint
White, E. (1996) · Genes & Development · doi:10.1101/gad.10.1.1 · Cited by 1,306
Fernandes‐Alnemri, T., Litwack, G., & Alnemri, E. S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47344-9 · Cited by 1,238
Hengartner, M. O., & Horvitz, H. R. (1994) · Cell · doi:10.1016/0092-8674(94)90506-1 · Cited by 1,167
Krajewski, S., Tanaka, S., Takayama, S., Schibler, M. J., Fenton, W. A., & Reed, J. C. (1993) · PubMed · Cited by 1,030
Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases
Rüegg, U. T., & Gillian, B. (1989) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(89)90263-0 · Cited by 904
Shrinkage necrosis: A distinct mode of cellular death
Kerr, J. R. (1971) · Journal of Pathology · doi:10.1002/path.1711050103 · Cited by 897
Caenorhabditis elegans gene ced-9 protects cells from programmed cell death
Hengartner, M. O., Ellis, R. E., & Horvitz, H. R. (1992) · Nature · doi:10.1038/356494a0 · Cited by 889
Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA
Jacobson, M. D., Burne, J. F., King, M. P., Miyashrta, T., Reed, J. C., & RAFF, M. C. (1993) · Nature · doi:10.1038/361365a0 · Cited by 751
Newmeyer, D. (1994) · Cell · doi:10.1016/0092-8674(94)90203-8 · Cited by 581
Yuan, J., & Horvitz, H. R. (1990) · Developmental Biology · doi:10.1016/0012-1606(90)90174-h · Cited by 536
Lazebnik, Y. A., Takahashi, A., Moir, R. D., Goldman, R. D., Poirier, G. G., Kaufmann, S. H., & Earnshaw, W. C. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9042 · Cited by 508
Schlegel, J., Peters, I., Orrenius, S., Miller, D. K., Thornberry, N. A., Yamin, T.-T., & Nicholson, D. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.4.1841 · Cited by 467
Xue, D., & Horvitz, H. R. (1995) · Nature · doi:10.1038/377248a0 · Cited by 463
Lazebnik, Y. A., Cole, S., Cooke, C. A., Nelson, W. G., & Earnshaw, W. C. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.1.7 · Cited by 445
Casciola-Rosen, L. A., Miller, D. K., Anhalt, G. J., & Rosen, A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47343-7 · Cited by 418
Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family.
Fernandes‐Alnemri, T., Litwack, G., & Alnemri, E. S. (1995) · PubMed · Cited by 405
Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency.
Cohen, A. M., Hirschhorn, R., Horowitz, S. D., et al. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.1.472 · Cited by 402
Mch3, a novel human apoptotic cysteine protease highly related to CPP32.
Fernandes‐Alnemri, T., Takahashi, A., Armstrong, R., et al. (1995) · PubMed · Cited by 396
Ultrastructural localization of bcl-2 protein.
Monaghan, P., Robertson, D. M., Amos, T. A. S., Dyer, M. J. S., Mason, D. Y., & Greaves, M. F. (1992) · Journal of Histochemistry & Cytochemistry · doi:10.1177/40.12.1453000 · Cited by 351
Duan, H., Chinnaiyan, A. M., Hudson, P. L., Wing, J. P., He, W.-W., & Dixit, V. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.3.1621 · Cited by 319
Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis.
Wang, X., Zelenski, N. G., Yang, J., Sakai, J., Brown, M. S., & Goldstein, J. L. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00438.x · Cited by 312
Self-citationWang, X., Briggs, M. R., Hua, X., Yokoyama, C., Goldstein, J. L., & Brown, M. S. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85266-3 · Cited by 299
Self-citationCell‐free reconstitution of Fas‐, UV radiation‐ and ceramide‐induced apoptosis.
Martin, S. J., Newmeyer, D. D., Mathias, S., Farschon, D. M., Wang, H., Reed, J. C., Kolesnick, R., & Green, D. R. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00203.x · Cited by 237
[61] Cytochrome c from vertebrate and invertebrate sources
Margoliash, E., & Walasek, O. F. (1967) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(67)10064-5 · Cited by 210
Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells.
de Jong, D., Prins, F., Mason, D. Y., Reed, J. C., van Ommen, G. B., & Kluin, P. M. (1994) · PubMed · Cited by 188
Apoptosis by a cytosolic extract from Fas‐activated cells.
Enari, M., Hase, A., & Nagata, S. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00204.x · Cited by 163
Wang, X., Pai, J., Wiedenfeld, E. A., Medina, J. C., Slaughter, C. A., Goldstein, J. L., & Brown, M. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.30.18044 · Cited by 137
Self-citationTranslocation of Apocytochrome c across the Outer Membrane of Mitochondria
Mayer, A., Neupert, W., & Lill, R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.21.12390 · Cited by 118
Age-associated damage in mitochondrial DNA in human hearts
Hayakawa, M., Sugiyama, S., Hattori, K., Takasawa, M., & Ozawa, T. (1993) · Molecular and Cellular Biochemistry · doi:10.1007/bf00926859 · Cited by 112
The ins and outs of programmed cell death during C. elegans development
Hengartner, M. O., & Horvitz, H. R. (1994) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1994.0100 · Cited by 104
Liu, X., Kim, C. N., Pohl, J., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.23.13371 · Cited by 86
Self-citationBiogenesis of mitochondrialc-type cytochromes
Gonzales, D. H., & Neupert, W. (1990) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf00786929 · Cited by 81
p53 expression is required for thymocyte apoptosis induced by adenosine deaminase deficiency.
Benveniste, P. M., & Cohen, A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8373 · Cited by 75
PAI, J.-A., Brown, M. S., & Goldstein, J. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5437 · Cited by 71
Evans, M. J., & Scarpulla, R. C. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.24.9625 · Cited by 52
Deoxynucleoside Induces Neuronal Apoptosis Independent of Neurotrophic Factors
Wakade, A. R., Przywara, D. A., Palmer, K. C., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.30.17986 · Cited by 33
Jemmerson, R., Johnson, J. G., Burrell, E., et al. (1991) · European Journal of Immunology · doi:10.1002/eji.1830210122 · Cited by 31
Self-citationGoday, A., Simmonds, H. A., Morris, G. S., et al. (1985) · Biochemical Pharmacology · doi:10.1016/0006-2952(85)90734-8 · Cited by 14
Different functional boundaries for the major antigenic region of two cytochromes c.
Jemmerson, R., & Johnson, J. G. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4428 · Cited by 8
Self-citation
Research works printed but not linked: 2
- Kaufmann, 1993, Specific proteolytic cleavage of poly(ADP-ribose) polymerase, Cancer Res., 53, 3976
- Krajewski, 1993, Investigation of the subcellular distribution of the bcl-2 oncoprotein, Cancer Res., 53, 4701
Cited by
Sorted by citations
Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80434-1 · Cited by 7,289
Self-citationGalluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
Martinon, F., Burns, K., & Tschopp, J. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00599-3 · Cited by 6,066
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Schafer, F. Q., & Buettner, G. R. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00480-4 · Cited by 4,587
Metadata
- Authors
- Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X.
- Affiliations
- Emory University (US)
- University of Minnesota (US)
- Corresponding author
- Wang, Xiaodong
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1996-07
- Volume
- 86
- Issue
- 1
- Pages
- 147-157
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2149967205
- Cited by
- 5,167
- References
- 49
- Citations by year
- 2026: 39 · 2025: 73 · 2024: 90 · 2023: 86 · 2022: 103 · 2021: 101 · 2020: 98 · 2019: 104 · 2018: 110 · 2017: 120 · 2016: 121 · 2015: 127 · 2014: 134 · 2013: 171 · 2012: 154
- FWCI
- 93.27
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- apoptosis, cytochrome c, dATP, cell-free extracts, cytosol, mitochondrial release, immunodepletion, mitochondrial stability
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Antibodies, Monoclonal, Cell Extracts, Cell-Free System, Cysteine Endopeptidases, Cytochrome c Group, Cytosol, DNA, Enzyme Precursors, HeLa Cells, Humans, Molecular Sequence Data, Apoptosis, Caspases, Caspase 3
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 ›
Are you an author, or do you see a problem with this page? Request a review