Mitochondria—Judges and Executioners of Cell Death Sentences
Open accessAbstract
Apoptosis is a form of programmed cell death that is critical for basic human development and physiology. One of the more important surprises in cell biology in the last two decades is the extent to which mitochondria represent a physical point of convergence for many apoptosis-inducing signals in mammalian cells. Mitochondria not only adjudicate the decision of whether or not to commit to cell death, but also release toxic proteins culminating in widespread proteolysis, nucleolysis, and cell engulfment. Interactions among BCL-2 family proteins at the mitochondrial outer membrane control the release of these toxic proteins and, by extension, control cellular commitment to apoptosis. This pathway is particularly relevant to cancer treatment, as most cancer chemotherapies trigger mitochondrial-mediated apoptosis. In this Review, we discuss recent advances in the BCL-2 family interactions, their control by upstream factors, and how the mitochondria itself alters these interactions. We also highlight recent clinical insights into mitochondrial-mediated apoptosis and novel cancer therapies that exploit this pathway.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Different BH3-only proteins preferentially bind specific anti-apoptotic BCL2 family members (e.g., BID, BIM, and PUMA potently bind all anti-apoptotic BCL2 family members; BAD preferentially interacts with BCL2, BCL-XL, and BCL-W; NOXA preferentially inhibits MCL1; and HRK preferentially inhibits BCL-XL).
“Different BH3-only proteins have been suggested to preferentially bind specific anti-apoptotic BCL2 family members (e.g., BID, BIM, and PUMA potently bind all anti-apoptotic BCL2 family members; BAD preferentially interacts with BCL2, BCL-XL, and BCL-W; NOXA preferentially inhibits MCL1; and HRK preferentially inhibits BCL-XL) [57, 113, 114].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [114]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992 · see citing works
RetractedHanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673 · see citing works
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 · see citing works
Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
Oltval, Z. N., Milliman, C. L., & Korsmeyer, S. J. (1993) · Cell · doi:10.1016/0092-8674(93)90509-o · Cited by 6,003 · 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
Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,120 · see citing works
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651 · see citing works
Cleavage 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
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
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990) · Nature · doi:10.1038/348334a0 · Cited by 3,720 · 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
miR-15 and miR-16 induce apoptosis by targeting BCL2
Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506654102 · Cited by 3,510 · see citing works
Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
Vaux, D., Cory, S., & Adams, J. (1988) · Nature · doi:10.1038/335440a0 · Cited by 3,355 · see citing works
Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy
Czabotar, P. E., Lessene, G., Strasser, A., & Adams, J. M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3722 · Cited by 3,219 · see citing works
Zou, H., Henzel, W. J., Liu, X., Lutschg, A., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80501-2 · Cited by 3,145 · see citing works
bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
Boise, L., González‐García, M., Postema, C. E., Ding, L., Lindsten, T., Turka, L. A., Mao, X., Núñez, G., & Thompson, C. B. (1993) · Cell · doi:10.1016/0092-8674(93)90508-n · Cited by 3,089 · see citing works
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S. L., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3048 · Cited by 3,058 · see citing works
Ji, Y. (1993) · Cell · doi:10.1016/0092-8674(93)90485-9 · Cited by 2,497 · see citing works
PUMA, a Novel Proapoptotic Gene, Is Induced by p53
Nakano, K., & Vousden, K. H. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00214-3 · Cited by 2,315 · see citing works
Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy
Fulda, S., & Debatin, K.-M. (2006) · Oncogene · doi:10.1038/sj.onc.1209608 · Cited by 2,312 · see citing works
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280 · see citing works
Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis
Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T., & Tanaka, †. N. (2000) · Science · doi:10.1126/science.288.5468.1053 · Cited by 2,112 · see citing works
Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death
Yang, E., Zha, J., Jockel, J., Boise, L., Thompson, C. B., & Korsmeyer, S. J. (1995) · Cell · doi:10.1016/0092-8674(95)90411-5 · Cited by 2,101 · see citing works
ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor
Tse, C., Shoemaker, A. R., Adickes, J., Anderson, M. G., Chen, J., Jin, S., Johnson, E. F., Marsh, K. C., Mitten, M. J., Nimmer, P., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5836 · Cited by 1,992 · see citing works
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia
Roberts, A. W., Davids, M. S., Pagel, J. M., Kahl, B. S., Puvvada, S. D., Gerecitano, J. F., Kipps, T. J., Anderson, M. A., Brown, J. R., Gressick, L. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1513257 · Cited by 1,901 · see citing works
Genetic control of programmed cell death in the nematode C. elegans
Ellis, H. (1986) · Cell · doi:10.1016/0092-8674(86)90004-8 · Cited by 1,828 · see citing works
Chen, L., Willis, S. N., Wei, A., Smith, B. J., Fletcher, J. I., Hinds, M. G., Colman, P. M., Day, C. L., Adams, J. M., & Huang, D. C. S. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.030 · Cited by 1,816 · see citing works
Endonuclease G is an apoptotic DNase when released from mitochondria
Li, L. Y., Luo, X., & Wang, X. (2001) · Nature · doi:10.1038/35083620 · Cited by 1,787 · see citing works
Cheng, E. H. Y., Wei, M. C., Weiler, S., Flavell, R. A., Mak, T. W., Lindsten, T., & Korsmeyer, S. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00320-3 · Cited by 1,708 · see citing works
Letai, A., Bassik, M. C., Walensky, L. D., Sorcinelli, M. D., Weiler, S., & Korsmeyer, S. J. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00127-7 · Cited by 1,677 · see citing works
Self-citationA receptor for phosphatidylserine-specific clearance of apoptotic cells
Fadok, V. A., Bratton, D. L., Rose, D. M., Pearson, A. M., Ezekowitz, R. A. B., & Henson, P. M. (2000) · Nature · doi:10.1038/35011084 · Cited by 1,491 · see citing works
Lindsten, T., Ross, A. J., King, A., Zong, W.-X., Rathmell, J. C., Shiels, H. A., Ulrich, E., Waymire, K. G., Mahar, P., Frauwirth, K., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00136-2 · Cited by 1,489 · see citing works
Bid, Bax, and Lipids Cooperate to Form Supramolecular Openings in the Outer Mitochondrial Membrane
Kuwana, T., Mackey, M. R., Perkins, G. A., Ellisman, M. H., Latterich, M., Schneiter, R., Green, D. R., & Newmeyer, D. D. (2002) · Cell · doi:10.1016/s0092-8674(02)01036-x · Cited by 1,480 · see citing works
Structure of Bcl-x <sub>L</sub> -Bak Peptide Complex: Recognition Between Regulators of Apoptosis
Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E., Eberstadt, M., Yoon, H. S., Shuker, S. B., Chang, B. S., Minn, A. J., et al. (1997) · Science · doi:10.1126/science.275.5302.983 · Cited by 1,476 · see citing works
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
Muchmore, S. W., Sattler, M., Liang, H., Meadows, R. P., Harlan, J. E., Yoon, H. S., Nettesheim, D. G., Chang, B. S., Thompson, C. B., Wong, S., et al. (1996) · Nature · doi:10.1038/381335a0 · Cited by 1,467 · see citing works
Chipuk, J. E., Moldoveanu, T., Llambi, F., Parsons, M. J., & Green, D. R. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.01.025 · Cited by 1,432 · see citing works
PUMA Induces the Rapid Apoptosis of Colorectal Cancer Cells
Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W., & Vogelstein, B. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00213-1 · Cited by 1,282 · see citing works
Certo, M. V., Moore, V. D. G., Nishino, M., Wei, G., Korsmeyer, S. J., Armstrong, S. A., & Letai, A. G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.027 · Cited by 1,278 · see citing works
Self-citationtBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome cPreprint
Wei, M. C., Lindsten, T., Mootha, V. K., Weiler, S., Gross, A., Ashiya, M., Thompson, C. B., & Korsmeyer, S. J. (2000) · Genes & Development · doi:10.1101/gad.14.16.2060 · Cited by 1,265 · see citing works
Willis, S. N., Chen, L., Dewson, G., Wei, A. H., Naik, E., Fletcher, J. I., Adams, J. M., & Huang, D. C. S. (2005) · Genes & Development · doi:10.1101/gad.1304105 · Cited by 1,236 · see citing works
McDonnell, T. J., Deane, N., Platt, F. M., Nunez, G., Jaeger, U., McKearn, J. P., & Korsmeyer, S. J. (1989) · Cell · doi:10.1016/0092-8674(89)90174-8 · Cited by 1,213 · see citing works
Kuwana, T., Bouchier-Hayes, L., Chipuk, J. E., Bonzon, C., Sullivan, B. A., Green, D. R., & Newmeyer, D. D. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.02.003 · Cited by 1,185 · see citing works
Bakhshi, A., Jensen, J. P., Goldman, P., Wright, J. J., McBride, O. W., Epstein, A. L., & Korsmeyer, S. J. (1985) · Cell · doi:10.1016/s0092-8674(85)80070-2 · Cited by 1,177 · see citing works
Hengartner, M. O., & Horvitz, H. R. (1994) · Cell · doi:10.1016/0092-8674(94)90506-1 · Cited by 1,167 · see citing works
Bim: a novel member of the Bcl‐2 family that promotes apoptosis
O’Connor, L., Strasser, A., O’Reilly, L. A., Hausmann, G., Adams, J. M., Cory, S., & Huang, D. C. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.2.384 · Cited by 1,163 · see citing works
Cytosol-to-membrane redistribution of Bax and Bcl-X L during apoptosis
Hsu, Y., Wolter, K. G., & Youle, R. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3668 · Cited by 1,134 · see citing works
Apoptosis Initiated When BH3 Ligands Engage Multiple Bcl-2 Homologs, Not Bax or Bak
Willis, S. N., Fletcher, J. I., Kaufmann, T., van Delft, M. F., Chen, L., Czabotar, P. E., Ierino, H., Lee, E. F., Fairlie, W. D., Bouillet, P., et al. (2007) · Science · doi:10.1126/science.1133289 · Cited by 1,125 · see citing works
Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis
Gross, A., Jockel, J., Wei, M. C., & Korsmeyer, S. J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.14.3878 · Cited by 1,086 · see citing works
Konopleva, M. Y., Contractor, R., Tsao, T., Samudio, I. J., Ruvolo, P. P., Kitada, S., Deng, X., Zhai, D., Shi, Y.-X., Sneed, T. B., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.006 · Cited by 1,020 · see citing works
Tsujimoto, Y., Gorham, J. D., Cossman, J., Jaffe, E. S., & Croce, C. M. (1985) · Science · doi:10.1126/science.3929382 · Cited by 990 · see citing works
Calcium-dependent phospholipid scrambling by TMEM16F
Suzuki, J., Umeda, M., Sims, P. J., & Nagata, S. (2010) · Nature · doi:10.1038/nature09583 · Cited by 982 · see citing works
Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death
Baines, C. P., Kaiser, R. A., Sheiko, T., Craigen, W. J., & Molkentin, J. D. (2007) · Nature Cell Biology · doi:10.1038/ncb1575 · Cited by 971 · see citing works
MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.
Kozopas, K. M., Yang, T., Buchan, H. L., Zhou, P., & Craig, R. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3516 · Cited by 964 · see citing works
Cleary, M. L., & Sklar, J. L. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.21.7439 · Cited by 955 · see citing works
BID: a novel BH3 domain-only death agonist.Preprint
Wang, K., Yin, X., Chao, D. T., Milliman, C. L., & Korsmeyer, S. J. (1996) · Genes & Development · doi:10.1101/gad.10.22.2859 · Cited by 941 · see citing works
Control of mitochondrial apoptosis by the Bcl-2 family
Brunelle, J. K., & Letai, A. G. (2009) · Journal of Cell Science · doi:10.1242/jcs.031682 · Cited by 928 · see citing works
Self-citationThree-Dimensional Structure of the Apoptosome
Acehan, D., Jiang, X., Morgan, D. G., Heuser, J. E., Wang, X., & Akey, C. W. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00442-2 · Cited by 912 · see citing works
Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2
Strasser, A., Harris, A. W., Bath, M. L., & Cory, S. (1990) · Nature · doi:10.1038/348331a0 · Cited by 905 · see citing works
Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies
Kim, H., Rafiuddin-Shah, M., Tu, H.-C., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J.-D., & Cheng, E. H.-Y. (2006) · Nature Cell Biology · doi:10.1038/ncb1499 · Cited by 874 · see citing works
VDAC2 Inhibits BAK Activation and Mitochondrial Apoptosis
Cheng, E. H.-Y., Sheiko, T. V., Fisher, J. K., Craigen, W. J., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1083995 · Cited by 852 · see citing works
Roberts, A. W., Seymour, J. F., Brown, J. R., Wierda, W. G., Kipps, T. J., Khaw, S. L., Carney, D. A., He, S., Huang, D. C. S., Xiong, H., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.7898 · Cited by 833 · see citing works
Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1
Opferman, J. T., Letai, A. G., Beard, C., Sorcinelli, M. D., Ong, C. C., & Korsmeyer, S. J. (2003) · Nature · doi:10.1038/nature02067 · Cited by 801 · see citing works
Self-citationSensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7
Wertz, I. E., Kusam, S., Lam, C., Okamoto, T., Sandoval, W. N., Anderson, D. J., Helgason, E., Ernst, J. A., Eby, M., Liu, J., et al. (2011) · Nature · doi:10.1038/nature09779 · Cited by 784 · see citing works
Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
Pan, R. A., Hogdal, L. J., Benito, J. M., Bucci, D. M., Han, L., Borthakur, G. M., Cortes, J. E., DeAngelo, D. J., Debose, L., Mu, H. H., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0609 · Cited by 734 · see citing works
Self-citationMechanisms of Action of Bcl-2 Family Proteins
Shamas-Din, A., Kale, J., Leber, B., & Andrews, D. W. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008714 · Cited by 705 · see citing works
BAX activation is initiated at a novel interaction site
Gavathiotis, E., Suzuki, M., Davis, M. L., Pitter, K., Bird, G. H., Katz, S. G., Tu, H.-C., Kim, H., Cheng, E. H.-Y., Tjandra, N., et al. (2008) · Nature · doi:10.1038/nature07396 · Cited by 700 · see citing works
SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction
Inuzuka, H., Shaik, S., Onoyama, I., Gao, D., Tseng, A., Maser, R. S., Zhai, B., Wan, L., Gutiérrez, A., Lau, A. W., et al. (2011) · Nature · doi:10.1038/nature09732 · Cited by 635 · see citing works
Live to die another way: modes of programmed cell death and the signals emanating from dying cells
Fuchs, Y., & Steller, H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3999 · Cited by 632 · see citing works
Bcl-xL Retrotranslocates Bax from the Mitochondria into the Cytosol
Edlich, F., Banerjee, S., Suzuki, M., Cleland, M. M., Arnoult, D., Wang, C., Neutzner, A., Tjandra, N., & Youle, R. J. (2011) · Cell · doi:10.1016/j.cell.2011.02.034 · Cited by 630 · see citing works
Gandhi, L., Camidge, D. R., Ribeiro de Oliveira, M., Bonomi, P., Gandara, D., Khaira, D., Hann, C. L., McKeegan, E. M., Litvinovich, E., Hemken, P. M., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.6208 · Cited by 603 · see citing works
Stepwise Activation of BAX and BAK by tBID, BIM, and PUMA Initiates Mitochondrial Apoptosis
Kim, H., Tu, H.-C., Ren, D., Takeuchi, O., Jeffers, J. R., Zambetti, G. P., Hsieh, J. J.-D., & Cheng, E. H.-Y. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.030 · Cited by 600 · see citing works
Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy
Chonghaile, T. N., Sarosiek, K. A., Vo, T.-T. T., Ryan, J. A., Tammareddi, A., Moore, V. D. G., Deng, J., Anderson, K. C., Richardson, P. G. G., Tai, Y., et al. (2011) · Science · doi:10.1126/science.1206727 · Cited by 588 · see citing works
Self-citationXk-Related Protein 8 and CED-8 Promote Phosphatidylserine Exposure in Apoptotic Cells
Suzuki, J., Denning, D. P., Imanishi, E., Horvitz, H. R., & Nagata, S. (2013) · Science · doi:10.1126/science.1236758 · Cited by 573 · see citing works
Czabotar, P. E., Westphal, D., Dewson, G., Ma, S., Hockings, C., Fairlie, W. D., Lee, E. F., Yao, S., Robin, A. Y., Smith, B. J., et al. (2013) · Cell · doi:10.1016/j.cell.2012.12.031 · Cited by 573 · see citing works
Lovell, J. F., Billen, L. P., Bindner, S., Shamas‐Din, A., Fradin, C., Leber, B. F., & Andrews, D. W. (2008) · Cell · doi:10.1016/j.cell.2008.11.010 · Cited by 564 · see citing works
Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure
Segawa, K., Kurata, S., Yanagihashi, Y., Brummelkamp, T. R., Matsuda, F., & Nagata, S. (2014) · Science · doi:10.1126/science.1252809 · Cited by 528 · see citing works
Lockshin, R. A., & Williams, C. M. (1965) · Journal of Insect Physiology · doi:10.1016/0022-1910(65)90099-5 · Cited by 487 · see citing works
Ichim, G., Lopez, J., Ahmed, S. U., Muthalagu, N., Giampazolias, E., Delgado, M. E., Haller, M., Riley, J. S., Mason, S. M., Athineos, D., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.018 · Cited by 479 · see citing works
Bax-independent inhibition of apoptosis by Bcl-XL
Cheng, E. H. Y., Levine, B., Boise, L., Thompson, C. B., & Hardwick, J. M. (1996) · Nature · doi:10.1038/379554a0 · Cited by 474 · see citing works
Zha, H., Aimé, C., Sato, T., & Reed, J. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.13.7440 · Cited by 465 · see citing works
Leverson, J. D., Zhang, H., Chen, J., Tahir, S. K., Phillips, D. C., Xue, J., Nimmer, P., Jin, S., Smith, M., Xiao, Y., et al. (2015) · Cell Death & Disease · doi:10.1038/cddis.2014.561 · Cited by 440 · see citing works
Chipuk, J. E., McStay, G. P., Bharti, A., Kuwana, T., Clarke, C. J., Siskind, L. J., Obeid, L. M., & Green, D. R. (2012) · Cell · doi:10.1016/j.cell.2012.01.038 · Cited by 436 · see citing works
Perciavalle, R. M., Stewart, D. P., Koss, B. S., Lynch, J., Milasta, S., Bathina, M., Temirov, J. P., Harwig, M. C., Pelletier, S. W., Schuetz, J. D., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2488 · Cited by 407 · see citing works
×Phosphorylation of Bax Ser184 by Akt Regulates Its Activity and Apoptosis in Neutrophils
Gardai, S. J., Hildeman, D. A., Frankel, S., Whitlock, B. B., Frasch, S. C., Borregaard, N., Marrack, P., Bratton, D. L., & Henson, P. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400063200 · Cited by 402 · see citing works
Inohara, N., Ding, L., Chen, S., & Núñez, G. (1997) · The EMBO Journal · doi:10.1093/emboj/16.7.1686 · Cited by 392 · see citing works
Cell Killing by the Drosophila Gene reaper
White, K., Tahaoglu, E., & Steller, H. (1996) · Science · doi:10.1126/science.271.5250.805 · Cited by 387 · see citing works
Drug-Induced Death Signaling Strategy Rapidly Predicts Cancer Response to Chemotherapy
Montero, J., Sarosiek, K. A., DeAngelo, J. D., Maertens, O., Ryan, J., Ercan, D., Piao, H., Horowitz, N. S., Berkowitz, R. S., Matulonis, U., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.042 · Cited by 378 · see citing works
Self-citationBax forms multispanning monomers that oligomerize to permeabilize membranes during apoptosis
Annis, M. G., Soucie, E. L., Dlugosz, P. J., Cruz-Aguado, J. A., Penn, L. Z., Leber, B. F., & Andrews, D. W. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600675 · Cited by 377 · see citing works
Programmed cell death and apoptosis: origins of the theory
Lockshin, R. A., & Zakeri, Z. F. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35080097 · Cited by 361 · see citing works
Vo, T.-T. T., Ryan, J. A., Carrasco, R. D., Neuberg, D. S., Rossi, D. J., Stone, R. M., DeAngelo, D. J., Frattini, M. G., & Letai, A. G. (2012) · Cell · doi:10.1016/j.cell.2012.08.038 · Cited by 348 · see citing works
Self-citationMAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death
Prudent, J., Zunino, R., Sugiura, A., Mattie, S., Shore, G. C., & McBride, H. M. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.08.001 · Cited by 321 · see citing works
Post-embryonic development in the ventral cord of Caenorhabditis elegans
Sulston, J. (1976) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1976.0084 · Cited by 315 · see citing works
bcl-w, a novel member of the bcl-2 family, promotes cell survival.
Gibson, L., Holmgreen, S. P., Huang, D. C. S., Bernard, O., Copeland, N. G., Jenkins, N. A., Sutherland, G. R., Baker, E. K., Adams, J. M., & Cory, S. (1996) · PubMed · Cited by 307 · see citing works
Tang, H. L., Tang, H. M., Mak, K. H., Hu, S., Wang, S. S., Wong, K. M., Wong, C. S. T., Wu, H. Y., Law, H. T., Liu, K., et al. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-11-0926 · Cited by 293 · see citing works
Bax regulates primary necrosis through mitochondrial dynamics
Whelan, R. S., Konstantinidis, K., Wei, A.-C., Chen, Y., Reyna, D. E., Jha, S., Yang, Y., Calvert, J. W., Lindsten, T., Thompson, C. B., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201608109 · Cited by 290 · see citing works
Karch, J., Kwong, J. Q., Burr, A. R., Sargent, M. A., Elrod, J. W., Peixoto, P. M., Martinez-Caballero, S., Osinska, H., Cheng, E. H.-Y., Robbins, J., et al. (2013) · eLife · doi:10.7554/elife.00772 · Cited by 290 · cited 1× · see citing works
“Surprisingly, loss of BAX and BAK inhibits mitochondrial swelling and rupture following mPTP opening, indicating that some of the proteins involved in mitochondrial-mediated apoptosis may nonetheless affect the mPTP (Karch et al., 2013; Whelan et al., 2012).”
BIM expression in treatment-naive cancers predicts responsiveness to kinase inhibitors
Faber, A. C., Corcoran, R. B., Ebi, H., Sequist, L. V., Waltman, B. A., Chung, E., Incio, J., Digumarthy, S. R., Pollack, S. F., Song, Y., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0106 · Cited by 283 · see citing works
Chonghaile, T. N., Roderick, J. E., Glenfield, C., Ryan, J. A., Sallan, S. E., Silverman, L. B., Loh, M. L., Hunger, S. P., Wood, B. L., DeAngelo, D. J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0353 · Cited by 276 · see citing works
Self-citationBOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation
Llambi, F., Wang, Y.-M., Victor, B., Yang, M., Schneider, D. M., Gingras, S., Parsons, M. J., Zheng, J. H., Brown, S. A., Pelletier, S., et al. (2016) · Cell · doi:10.1016/j.cell.2016.02.026 · Cited by 261 · see citing works
An interconnected hierarchical model of cell death regulation by the BCL-2 family
Chen, H.-C., Kanai, M., Inoue-Yamauchi, A., Tu, H.-C., Huang, Y., Ren, D., Kim, H., Takeda, S., Reyna, D. E., Chan, P. M., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3236 · Cited by 249 · see citing works
Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation
Xin, M., & Deng, X. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500084200 · Cited by 246 · see citing works
Pyakurel, A., Savoia, C., Hess, D., & Scorrano, L. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.02.021 · Cited by 244 · see citing works
The Soluble Form of Bax Regulates Mitochondrial Fusion via MFN2 Homotypic Complexes
Hoppins, S. C., Edlich, F., Harwig, M. C., Banerjee, S., McCaffery, J. M., Youle, R. J., & Nunnari, J. M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2010.11.030 · Cited by 243 · see citing works
Sarosiek, K. A., Chi, X., Bachman, J. A., Sims, J. J., Montero, J., Patel, L., Flanagan, A., Andrews, D. W., Sorger, P. K., & Letai, A. G. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.048 · Cited by 242 · see citing works
Self-citationMultisite Phosphorylation Regulates Bim Stability and Apoptotic Activity
Hübner, A., Barrett, T., Flavell, R. A., & Davis, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.025 · Cited by 228 · see citing works
Structural Model of Active Bax at the Membrane
Bleicken, S., Jeschke, G., Stegmueller, C., Salvador-Gallego, R., García-Sáez, A. J., & Bordignon, E. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.022 · Cited by 227 · see citing works
Mitochondrial Shape Governs BAX-Induced Membrane Permeabilization and Apoptosis
Renault, T. T., Floros, K. V., Elkholi, R., Corrigan, K.-A., Kushnareva, Y., Wieder, S. Y., Lindtner, C., Serasinghe, M. N., Asciolla, J. J., Buettner, C., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2014.10.028 · Cited by 217 · see citing works
Different forms of cell death induced by putative BCL2 inhibitors
Vogler, M., Weber, K., Dinsdale, D. D., Schmitz, I., Schulze‐Osthoff, K., Dyer, M. J. S., & Cohen, G. M. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.48 · Cited by 203 · see citing works
BID-induced structural changes in BAK promote apoptosis
Moldoveanu, T., Grace, C. R., Llambi, F., Nourse, A., Fitzgerald, P., Gehring, K., Kriwacki, R. W., & Green, D. R. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2563 · Cited by 201 · see citing works
The multidomain proapoptotic molecules Bax and Bak are directly activated by heat
Pagliari, L. J., Kuwana, T., Bonzon, C., Newmeyer, D. D., Tu, S. S., Beere, H. M., & Green, D. R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506712102 · Cited by 185 · see citing works
Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w
Wang, J., Gao, J., Ding, S.-L., Wang, K., Jiao, J.-Q., Wang, Y., Sun, T., Zhou, L., Long, B., Zhang, X.-J., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.05.003 · Cited by 184 · see citing works
Souers, A. J., Leverson, J. D., Boghaert, E. R., Ackler, S., Catron, N. D., Chen, J., Dayton, B. D., Ding, H., Enschede, S. H., Fairbrother, W. J., et al. (2013) · Cited by 180 · see citing works
Distinct pathways mediate axon degeneration during apoptosis and axon-specific pruning
Cusack, C. L., Swahari, V., Henley, W. H., Ramsey, J. M., & Deshmukh, M. (2013) · Nature Communications · doi:10.1038/ncomms2910 · Cited by 176 · see citing works
BH3 Domains other than Bim and Bid Can Directly Activate Bax/Bak
Du, H., Wolf, J., Schafer, B., Moldoveanu, T., Chipuk, J. E., & Kuwana, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.167148 · Cited by 165 · see citing works
Brouwer, J. M., Westphal, D., Dewson, G., Robin, A. Y., Uren, R. T., Bartolo, R., Thompson, G. V., Colman, P. M., Kluck, R. M., & Czabotar, P. E. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.07.016 · Cited by 161 · see citing works
Dai, H., Smith, A., Meng, X. W., Schneider, P. A., Pang, Y.-P., & Kaufmann, S. H. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102027 · Cited by 159 · see citing works
Dumitru, R., Gama, V., Fagan, B. M., Bower, J. J., Swahari, V., Pevny, L., & Deshmukh, M. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.002 · Cited by 157 · see citing works
Direct activation of full-length proapoptotic BAK
Leshchiner, E. S., Braun, C. R., Bird, G. H., & Walensky, L. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214313110 · Cited by 157 · see citing works
Lowman, X. H., McDonnell, M. A., Kosloske, A. M., Odumade, O. A., Jenness, C., Karim, C. B., Jemmerson, R., & Kelekar, A. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.11.035 · Cited by 155 · see citing works
Roy, S. S., Ehrlich, A. M., Craigen, W. J., & Hajnóczky, G. (2009) · EMBO Reports · doi:10.1038/embor.2009.219 · Cited by 146 · see citing works
Mst1 Promotes Cardiac Myocyte Apoptosis through Phosphorylation and Inhibition of Bcl-xL
Re, D. P. D., Matsuda, T., Zhai, P., Maejima, Y., Jain, M. R., Liu, T., Li, H., Hsu, C., & Sadoshima, J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.04.007 · Cited by 136 · see citing works
Davids, M. S., Deng, J., Wiestner, A. U., Lannutti, B. J., Wang, L., Wu, C. J., Wilson, W. H., Brown, J. R., & Letai, A. G. (2012) · Blood · doi:10.1182/blood-2012-02-414060 · Cited by 136 · see citing works
Self-citationRyan, J. A., Brunelle, J. K., & Letai, A. G. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914878107 · Cited by 128 · see citing works
Self-citationBCL-2 family member BOK promotes apoptosis in response to endoplasmic reticulum stress
Carpio, M. A., Michaud, M., Zhou, W., Fisher, J. K., Walensky, L. D., & Katz, S. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421063112 · Cited by 127 · see citing works
In vivo CaspaseTracker biosensor system for detecting anastasis and non-apoptotic caspase activity
Tang, H. L., Tang, H. M., Fung, M. C., & Hardwick, J. M. (2015) · Scientific Reports · doi:10.1038/srep09015 · Cited by 115 · see citing works
Regulation of Bcl-2 Family Proteins by Posttranslational Modifications
Letai, A. G., & Kütük, Ö. (2008) · Current Molecular Medicine · doi:10.2174/156652408783769599 · Cited by 108 · see citing works
Self-citationLindner, A. U., Concannon, C. G., Boukes, G. J., Cannon, M. D., Llambi, F., Ryan, D., Boland, K., Kehoe, J., McNamara, D. A., Murray, F., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2269 · Cited by 105 · see citing works
Aranovich, A., Liu, Q., Collins, T., Geng, F., Dixit, S., Leber, B. F., & Andrews, D. W. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.030 · Cited by 103 · see citing works
Evolution of Bcl-2 homology motifs: homology versus homoplasy
Aouacheria, A., Rech de Laval, V., Combet, C., & Hardwick, J. M. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.10.010 · Cited by 103 · see citing works
Evaluation and critical assessment of putative MCL-1 inhibitors
Varadarajan, S., Vogler, M., Butterworth, M., Dinsdale, D. D., Walensky, L. D., & Cohen, G. M. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.79 · Cited by 101 · see citing works
Pin1-Induced Proline Isomerization in Cytosolic p53 Mediates BAX Activation and Apoptosis
Follis, A. V., Llambi, F., Merritt, P., Chipuk, J. E., Green, D. R., & Kriwacki, R. W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.06.029 · Cited by 96 · see citing works
Distinct lipid effects on tBid and Bim activation of membrane permeabilization by pro-apoptotic Bax
Shamas‐Din, A., Bindner, S., Chi, X., Leber, B. F., Andrews, D. W., & Fradin, C. (2015) · Biochemical Journal · doi:10.1042/bj20141291 · Cited by 72 · see citing works
Visual and functional demonstration of growing Bax-induced pores in mitochondrial outer membranes
Gillies, L. A., Du, H., Peters, B., Knudson, C. M., Newmeyer, D. D., & Kuwana, T. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-11-0638 · Cited by 60 · see citing works
Tyrosine dephosphorylation is required for Bak activation in apoptosis
Fox, J. L., Ismail, F., Azad, A. K., Ternette, N., Leverrier, S., Edelmann, M. J., Kessler, B. M., Leigh, I. M., Jackson, S., & Storey, A. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.244 · Cited by 47 · see citing works
An intracellular wave of cytochrome c propagates and precedes Bax redistribution during apoptosis
Lartigue, L., Medina, C. F., Schembri, L., Chabert, P., Zanese, M., Tomasello, M. F., Dalibart, R., Thoraval, D. H., Crouzet, M., Ichas, F., et al. (2008) · Journal of Cell Science · doi:10.1242/jcs.029587 · Cited by 46 · see citing works
Spatial and Temporal Dynamics of Mitochondrial Membrane Permeability Waves during Apoptosis
Bhola, P. D., Mattheyses, A. L., & Simon, S. M. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.07.056 · Cited by 45 · see citing works
Self-citationGenome-wide prediction and validation of peptides that bind human prosurvival Bcl-2 proteins
DeBartolo, J., Taipale, M., & Keating, A. E. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003693 · Cited by 39 · see citing works
The apoptotic pore on mitochondria: are we breaking through or still stuck?
Borner, C., & Andrews, D. W. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2013.169 · Cited by 30 · see citing works
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
Microglia monitor and protect neuronal function through specialized somatic purinergic junctions
Cserép, C., Pósfai, B., Lénárt, N., Fekete, R., László, Z. I., Lele, Z., Orsolits, B., Molnár, G., Heindl, S., Schwarcz, A. D., et al. (2020) · Science · doi:10.1126/science.aax6752 · Cited by 684 · see citing works
Kurppa, K. J., Liu, Y., To, C., Zhang, T., Fan, M., Vajdi, A., Knelson, E. H., Xie, Y., Lim, K., Cejas, P., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2019.12.006 · Cited by 475 · see citing works
Functional precision cancer medicine—moving beyond pure genomics
Letai, A. (2017) · Nature Medicine · doi:10.1038/nm.4389 · Cited by 366 · see citing works
Self-citationRottenberg, H., & Hoek, J. B. (2017) · Aging Cell · doi:10.1111/acel.12650 · Cited by 275 · see citing works
Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions
Cserép, C., Pósfai, B., & Dénes, Á. (2021) · Neuron · doi:10.1016/j.neuron.2020.11.007 · Cited by 256 · see citing works
Dela Cruz, C. S., & Kang, M.-J. (2018) · Mitochondrion · doi:10.1016/j.mito.2017.12.001 · Cited by 255 · see citing works
A BH3 Mimetic for Killing Cancer Cells
Green, D. R. (2016) · Cell · doi:10.1016/j.cell.2016.05.080 · Cited by 79 · see citing works
Xiao, L., Chen, B., Wang, W., Tian, T., Qian, H., Li, X., & Yu, Y. (2023) · Advanced Science · doi:10.1002/advs.202302141 · Cited by 64 · see citing works
Knickelbein, K., Tong, J., Chen, D., Wang, Y.-J., Misale, S., Bardelli, A., Yu, J., & Zhang, L. (2018) · Oncogene · doi:10.1038/s41388-018-0289-x · Cited by 33 · see citing works
- Authors
- Bhola, P. D., & Letai, A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Letai, Anthony
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 61
- Issue
- 5
- Pages
- 695-704
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4806554
- OpenAlex
- W2289284908
- Cited by
- 326
- References
- 140
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 17 · 2023: 38 · 2022: 21 · 2021: 36 · 2020: 42 · 2019: 50 · 2018: 46 · 2017: 30 · 2016: 24
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R21CA188858, P01CA066996)
- 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
- apoptosis, mitochondria, Bcl-2 family proteins, mitochondrial outer membrane, programmed cell death, cancer chemotherapy, cancer therapy
- MeSH terms
- Mitochondrial Permeability Transition Pore, Animals, Antineoplastic Agents, Humans, Mitochondria, Neoplasms, Permeability, Protein Binding, Signal Transduction, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Mitochondrial Membrane Transport Proteins, Apoptosis Regulatory Proteins, Mitochondrial Membranes, Protein Interaction Domains and Motifs, Molecular Targeted Therapy
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
