Cytochrome c Deficiency Causes Embryonic Lethality and Attenuates Stress-Induced Apoptosis
Open accessAbstract
Cytochrome c released from mitochondria has been proposed to be an essential component of an apoptotic pathway responsive to DNA damage and other forms of cell stress. Murine embryos devoid of cytochrome c die in utero by midgestation, but cell lines established from early cytochrome c null embryos are viable under conditions that compensate for defective oxidative phosphorylation. As compared to cell lines established from wild-type embryos, cells lacking cytochrome c show reduced caspase-3 activation and are resistant to the proapoptotic effects of UV irradiation, serum withdrawal, or staurosporine. In contrast, cells lacking cytochrome c demonstrate increased sensitivity to cell death signals triggered by TNFalpha. These results define the role of cytochrome c in different apoptotic signaling cascades.
Integrity signals
Registry
Cites
Statistics
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?
MOMP directly promotes the cytosolic release of apoptogenic factors that normally reside in the mitochondrial intermembrane space, including cytochrome c (CYCS) and SMAC.
“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 [159]
Cites
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 8,998 · see citing works
Thornberry, N. A., & Lazebnik, Y. A. (1998) · Science · doi:10.1126/science.281.5381.1312 · Cited by 6,857 · see citing works
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 6,535 · see citing works
Chelex 100 as a Medium for Simple Extraction of DNA for PCR-Based Typing from Forensic Material
Walsh, P. S., Metzger, D. A., & Higuchi, R. (2013) · BioTechniques · doi:10.2144/000114018 · Cited by 5,850 · see citing works
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996) · Cell · doi:10.1016/s0092-8674(00)80085-9 · Cited by 5,167 · see citing works
Self-citationCleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis
Li, H., Zhu, H., Xu, C.-J., & Yuan, J. (1998) · Cell · doi:10.1016/s0092-8674(00)81590-1 · Cited by 4,445 · see citing works
Molecular characterization of mitochondrial apoptosis-inducing factor
Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., et al. (1999) · Nature · doi:10.1038/17135 · Cited by 4,060 · see citing works
Luo, X., Budihardjo, I., Zou, H., Slaughter, C., & Wang, X. (1998) · Cell · doi:10.1016/s0092-8674(00)81589-5 · Cited by 3,626 · see citing works
Self-citationSuppression of TNF-α-Induced Apoptosis by NF-κB
Antwerp, D. J. V., Martin, S. J., Kafri, T., Green, D. R., & Verma, I. M. (1996) · Science · doi:10.1126/science.274.5288.787 · Cited by 2,581 · see citing works
Emmert‐Buck, M. R., Bonner, R. F., Smith, P. D., Chuaqui, R. F., Zhuang, Z., Goldstein, S. R., Weiss, R. A., & Liotta, L. A. (1996) · Science · doi:10.1126/science.274.5289.998 · Cited by 2,540 · see citing works
An APAF-1·Cytochrome c Multimeric Complex Is a Functional Apoptosome That Activates Procaspase-9
Zou, H., Li, Y., Liu, X., & Wang, X. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.11549 · Cited by 2,089 · see citing works
Self-citationTHE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS
Kroemer, G., Dallaporta, B., & Resche-Rigon, M. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.619 · Cited by 1,971 · see citing works
Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
Kuida, K., Zheng, T. S., Na, S., Kuan, C.-Y., Yang, D., Karasuyama, H., RAKIC, P. T., & Flavell, R. A. (1996) · Nature · doi:10.1038/384368a0 · Cited by 1,881 · see citing works
Human Cells Lacking mtDNA: Repopulation with Exogenous Mitochondria by Complementation
King, M. P., & Attardi, G. M. (1989) · Science · doi:10.1126/science.2814477 · Cited by 1,659 · see citing works
Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9
Kuida, K., Haydar, T. F., Kuan, C.-Y., Gu, Y., Taya, C., Karasuyama, H., Su, M. S.-S., Rakic, P., & Flavell, R. A. (1998) · Cell · doi:10.1016/s0092-8674(00)81476-2 · Cited by 1,643 · see citing works
Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice
Larsson, N.-G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G. S., & Clayton, D. A. (1998) · Nature Genetics · doi:10.1038/ng0398-231 · Cited by 1,594 · see citing works
Vaux, D. L., & Korsmeyer, S. J. (1999) · Cell · doi:10.1016/s0092-8674(00)80564-4 · Cited by 1,564 · see citing works
Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation
(1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90040-d · Cited by 1,386 · see citing works
Differential Requirement for Caspase 9 in Apoptotic Pathways In Vivo
Hakem, R., Hakem, A., Duncan, G. S., Henderson, J. T., Woo, M., Soengas, M. S., Elia, A., de la Pompa, J. L., Kägi, D., Khoo, W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81477-4 · Cited by 1,284 · see citing works
Apaf1 Is Required for Mitochondrial Pathways of Apoptosis and Brain Development
Yoshida, H., Kong, Y., Yoshida, R., Elia, A., Hakem, A., Hakem, R., Penninger, J. M., & Mak, T. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81733-x · Cited by 1,138 · see citing works
Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis
Yin, X.-M., Wang, K., Gross, A., Zhao, Y., Zinkel, S., Klocke, B., Roth, K. A., & Korsmeyer, S. J. (1999) · Nature · doi:10.1038/23730 · Cited by 1,004 · see citing works
Apaf1 (CED-4 Homolog) Regulates Programmed Cell Death in Mammalian Development
Cecconi, F., Álvarez-Bolado, G., Meyer, B. I., Roth, K. A., & Gruß, P. (1998) · Cell · doi:10.1016/s0092-8674(00)81732-8 · Cited by 894 · see citing works
Laser Capture Microdissection: Molecular Analysis of Tissue
Bonner, R. F., Emmert‐Buck, M. R., Cole, K. A., Pohida, T. J., Chuaqui, R. F., Goldstein, S. R., & Liotta, L. A. (1997) · Science · doi:10.1126/science.278.5342.1481 · Cited by 877 · see citing works
Fisher, C. R., Graves, K. H., Parlow, A. F., & Simpson, E. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6965 · Cited by 867 · see citing works
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changesPreprint
Woo, M., Hakem, R., Soengas, M. S., Duncan, G. S., Shahinian, A., Kägi, D., Hakem, A., McCurrach, M. E., Khoo, W., Kaufman, S. A., et al. (1998) · Genes & Development · doi:10.1101/gad.12.6.806 · Cited by 832 · see citing works
Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J., LeBlanc, A. C., Smith, D., Rigby, M., Shearman, M. S., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80748-5 · Cited by 784 · see citing works
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 · see citing works
Narula, J., Pandey, P., Arbustini, E., Haider, N., Narula, N., Kolodgie, F. D., Bello, B. D., Semigran, M. J., Bielsa-Masdeu, A., Dec, G. W., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.8144 · Cited by 586 · see citing works
Erratum: Overview of the yeast genome
Mewes, H., Albermann, K., Bähr, M., Frishman, D., Gleißner, A., Hani, J., Heumann, K., Kleine, K., Maierl, A., Oliver, S. G., et al. (1997) · Nature · doi:10.1038/42755 · Cited by 526 · see citing works
Kluck, R. M., Martin, S. J., Hoffman, B. M., Zhou, J. S., Green, D. R., & Newmeyer, D. D. (1997) · The EMBO Journal · doi:10.1093/emboj/16.15.4639 · Cited by 383 · see citing works
Injected cytochrome c induces apoptosis
Zhivotovsky, B., Orrenius, S., Brustugun, O. T., & Døskeland, S. O. (1998) · Nature · doi:10.1038/35060 · Cited by 351 · see citing works
Mitochondrial Depolarization Accompanies Cytochrome cRelease During Apoptosis in PC6 Cells
Heiskanen, K. M., Bhat, M. B., Wang, H.-W., Ma, J., & Nieminen, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.9.5654 · Cited by 348 · see citing works
Cell-specific Induction of Apoptosis by Microinjection of Cytochrome c
Li, F., Srinivasan, A. N., Wang, Y., Armstrong, R. C., Tomaselli, K. J., & Fritz, L. C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.48.30299 · Cited by 347 · see citing works
Rodriguez, A., Oliver, H., Zou, H., Chen, P., Wang, X., & Abrams, J. (1999) · Nature Cell Biology · doi:10.1038/12984 · Cited by 332 · see citing works
Self-citationStress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3
Nishina, H., Fischer, K., Radvanyi, L. G., Shahinian, A., Hakem, R., Rubie, E. A., Bernstein, A., Mak, T. W., Woodgett, J. R., & Penninger, J. M. (1997) · Nature · doi:10.1038/385350a0 · Cited by 323 · see citing works
Structure and Function of Cytochromes C
Salemme, F. R. (1977) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.46.070177.001503 · Cited by 283 · see citing works
[49] Derivation of embryonic stem cell lines
Abbondanzo, S. J., Gadi, I. K., & Stewart, C. L. (1993) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(93)25052-4 · Cited by 225 · see citing works
Cytochrome c-mediated Apoptosis in Cells Lacking Mitochondrial DNA
Jiang, S., Cai, J., Wallace, D. C., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.29905 · Cited by 165 · see citing works
Sabbah, H., & Sharov, V. G. (1998) · Progress in cardiovascular diseases · doi:10.1016/s0033-0620(98)80003-0 · Cited by 142 · see citing works
Suzuki, A., Tsutomi, Y., Yamamoto, N., Shibutani, T., & Akahane, K. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3842 · Cited by 131 · see citing works
Hake, L. E., Alcivar, A. A., & Hecht, N. B. (1990) · Development · doi:10.1242/dev.110.1.249 · Cited by 64 · see citing works
Hake, L. E., & Hecht, N. B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53466-9 · Cited by 51 · see citing works
Characterization of a mouse somatic cytochrome c gene and three cytochrome c pseudogenes
Limbach, K. J., & Wu, R. (1985) · Nucleic Acids Research · doi:10.1093/nar/13.2.617 · Cited by 45 · see citing works
Cloning and Characterization of Three New Murine Genes Encoding Short Homologues of RNase P RNA
Li, K., & Williams, R. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.25281 · Cited by 23 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, 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 · see citing works
Signal transduction by the JNK group of MAP kinases
Davis, R. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00116-1 · Cited by 4,237 · see citing works
The Bcl2 family: regulators of the cellular life-or-death switch
Cory, S., & Adams, J. M. (2002) · Nature Reviews Cancer · doi:10.1038/nrc883 · Cited by 4,032 · see citing works
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Wei, M. C., Zong, W.-X., Cheng, E. H.-Y., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., & Korsmeyer, S. J. (2001) · Science · doi:10.1126/science.1059108 · Cited by 3,988 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Mitochondria and cell death: outer membrane permeabilization and beyond
Tait, S. W. G., & Green, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2952 · Cited by 2,593 · see citing works
Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421 · see citing works
The Role of Mitochondria in Apoptosis
Wang, C., & Youle, R. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102108-134850 · Cited by 1,987 · see citing works
The Role of Dynamin-Related Protein 1, a Mediator of Mitochondrial Fission, in Apoptosis
Frank, S., Gaume, B., Bergmann-Leitner, E. S., Leitner, W. W., Robert, E. G., Catez, F., Smith, C. L., & Youle, R. J. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00055-7 · Cited by 1,755 · see citing works
Gottlob, K., Majewski, N., Kennedy, S., Kandel, E., Robey, R. B., & Hay, N. (2001) · Genes & Development · doi:10.1101/gad.889901 · Cited by 961 · see citing works
Guzy, R. D., & Schumacker, P. T. (2006) · Experimental Physiology · doi:10.1113/expphysiol.2006.033506 · Cited by 881 · see citing works
Mansfield, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T., & Simon, M. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.003 · Cited by 606 · see citing works
Mitochondrial Regulation of Cell Death
Tait, S. W. G., & Green, D. R. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008706 · Cited by 530 · see citing works
Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice
Cerritelli, S. M., Frolova, E. G., Feng, C., Grinberg, A., Love, P. E., & Crouch, R. J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00088-1 · Cited by 358 · see citing works
Dixon, S. J. (2017) · Immunological Reviews · doi:10.1111/imr.12533 · Cited by 314 · see citing works
Increased <i>in vivo</i> apoptosis in cells lacking mitochondrial DNA gene expression
Wang, J., Silva, J. P., Gustafsson, C. M., Rustin, P., & Larsson, N.-G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061038798 · Cited by 245 · see citing works
Sleep-dependent activity of T cells and regulatory T cells
Bollinger, T., Bollinger, A., Skrum, L., Dimitrov, S., Lange, T., & Solbach, W. (2009) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2008.03822.x · Cited by 167 · see citing works
TERT promotes cellular and organismal survival independently of telomerase activity
Lee, J., Sung, Y. H., Cheong, C., Choi, Y. S., Jeon, H. K., Sun, W., Hahn, W. C., Ishikawa, F., & Lee, H.-W. (2008) · Oncogene · doi:10.1038/sj.onc.1211037 · Cited by 145 · see citing works
Non‐apoptotic functions of apoptosis‐regulatory proteins
Galluzzi, L., Kepp, O., Trojel‐Hansen, C., & Kroemer, G. (2012) · The EMBO Reports · doi:10.1038/embor.2012.19 · Cited by 109 · see citing works
Jiang, D., Fu, C., Xiao, J., Zhang, Z., Zou, J., Ye, Z., & Zhang, X. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2013594 · Cited by 31 · see citing works
- Authors
- Li, K., Li, Y., Shelton, J. M., Richardson, J. A., Spencer, E., Chen, Z. J., Wang, X., & Williams, R. S.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Williams, R.Sanders
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2000-05
- Volume
- 101
- Issue
- 4
- Pages
- 389-399
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2025713422
- Cited by
- 509
- References
- 44
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 14 · 2023: 10 · 2022: 7 · 2021: 15 · 2020: 10 · 2019: 13 · 2018: 10 · 2017: 7 · 2016: 16 · 2015: 14 · 2014: 12 · 2013: 15 · 2012: 20
- FWCI
- 18.82
- 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
- cytochrome c, embryonic lethality, apoptosis, mitochondrial apoptosis, caspase-3 activation, TNF-alpha-induced cell death, UV-induced apoptosis, staurosporine, oxidative phosphorylation, DNA damage, stress-induced cell death
- MeSH terms
- Animals, Cytochrome c Group, Embryo, Mammalian, Embryonic and Fetal Development, Apoptosis, Gene Expression Regulation, Developmental, Embryo Loss, Mice
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
