Intracellular adenosine triphosphate (ATP) concentration: A switch in the decision between apoptosis and necrosis
Open accessAbstract
Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) changed from apoptosis to necrosis, when cells were preemptied of adenosine triphosphate (ATP). Nuclear condensation and DNA fragmentation did not occur in cells predepleted of ATP and treated with either of the two inducers, although the kinetics of cell death were unchanged. Selective and graded repletion of the extramitochondrial ATP/pool with glucose prevented necrosis and restored the ability of the cells to undergo apoptosis. Pulsed ATP/depletion/repletion experiments also showed that ATP generation either by glycolysis or by mitochondria was required for the active execution of the final phase of apoptosis, which involves nuclear condensation and DNA degradation.
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?
On reperfusion, cardiac muscle cells are further injured because mitochondria produce large quantities of ROS due to massive electron leaks and superoxide formation with resupplied oxygen, which denatures cytosolic enzymes and destroys cell membranes by lipid peroxidation.
“On reperfusion, the cardiac muscle cells are further injured, because in the mitochondria, ROS are produced in large quantities due to massive electron leaks and the formation of superoxide with the resupplied oxygen, which denatures cytosolic enzymes and destroys cell membranes by lipid peroxidation.”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [93]
ROS-mediated dysfunction of the sarcoplasmic reticulum induces massive intracellular calcium overload, leading to opening of the mitochondrial permeability transition pore and causing cell apoptosis or necrosis depending on intracellular ATP levels.
“ROS-mediated dysfunction of the sarcoplasmic reticulum also induces massive intracellular calcium overload, leading to the opening of the mitochondrial permeability transition pore and causing cell apoptosis or necrosis, depending on the intracellular ATP levels [93,94].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [93]
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
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078 · see citing works
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 7,235 · see citing works
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
Wyllie, A. H. (1980) · Nature · doi:10.1038/284555a0 · Cited by 4,549 · see citing works
Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J. D., Zhang, M., Gentz, R., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81266-0 · Cited by 3,046 · see citing works
Boldin, M. P., Goncharov, T. M., Goltseve, Y. V., & Wallach, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81265-9 · Cited by 2,292 · see citing works
Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., & Lipton, S. A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7162 · Cited by 1,958 · see citing works
Self-citationAnkarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., & Nicotera, P. (1995) · Neuron · doi:10.1016/0896-6273(95)90186-8 · Cited by 1,884 · see citing works
Self-citationMonoclonal Antibody-Mediated Tumor Regression by Induction of Apoptosis
Trauth, B. C., Klas, C., Peters, A. M. J., Matzku, S., Mӧller, P., Falk, W., Debatin, K., & Krammer, P. H. (1989) · Science · doi:10.1126/science.2787530 · Cited by 1,716 · see citing works
Yonehara, S., Ishii, A., & Yonehara, M. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.5.1747 · Cited by 1,398 · see citing works
Mitochondrial control of nuclear apoptosis.
Zamzami, N., Susín, S. A., Marchetti, P., Hirsch, T., Gomez-Monterrey, I. M., Castedo, M., & Kroemer, G. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.4.1533 · Cited by 1,360 · see citing works
Bcl-2 inhibits the mitochondrial release of an apoptogenic protease.
Susín, S. A., Zamzami, N., Castedo, M., Hirsch, T., Marchetti, P., Macho, A., Daugas, É., Geuskens, M., & Kroemer, G. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1331 · Cited by 1,133 · 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
Programmed cell death and Bcl-2 protection in very low oxygen
Jacobson, M. D., & RAFF, M. C. (1995) · Nature · doi:10.1038/374814a0 · Cited by 625 · see citing works
bcl-2 inhibits death of central neural cells induced by multiple agents.
Zhong, L. T., Sarafian, T. A., Kane, D. J., Charles, A. C., Mah, S. P., Edwards, R. H., & Bredesen, D. E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4533 · Cited by 619 · see citing works
Programmed cell death and Bcl‐2 protection in the absence of a nucleus.
Jacobson, M. D., Burne, J. F., & RAFF, M. C. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06459.x · Cited by 548 · see citing works
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 · see citing works
Leist, M., Gantner, F., Bohlinger, I., Tiegs, G., Germann, P., & Wendel, A. (1995) · Europe PMC (PubMed Central) · Cited by 493 · see citing works
Self-citationLeist, M., Gantner, F., Bohlinger, I., Germann, P., Tiegs, G., & Wendel, A. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.153.4.1778 · Cited by 492 · see citing works
Self-citationControl of apoptosis by the cellular ATP level
Richter, C., Schweizer, M., Cossarizza, A., & Franceschi, C. (1996) · FEBS Letters · doi:10.1016/0014-5793(95)01431-4 · Cited by 470 · see citing works
Constitutive expression of the machinery for programmed cell death.
Weil, M., Jacobson, M. D., Coles, H., Davies, T. J., Gardner, R. L., Raff, K., & RAFF, M. C. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.133.5.1053 · Cited by 383 · see citing works
Shimizu, S., Eguchi, Y., Kamiike, W., Itoh, Y., Hasegawa, J., Yamabe, K., Otsuki, Y., Matsuda, H., & Tsujimoto, Y. (1996) · PubMed · Cited by 361 · see citing works
Dypbukt, J. M., Ankarcrona, M., Burkitt, M. J., Sjöholm, Å., Ström, K., Orrenius, S., & Nicotera, P. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43849-5 · Cited by 361 · see citing works
Self-citationOberhammer, F., Hochegger, K., Fröschl, G., Tiefenbacher, R., & Pavelka, M. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.126.4.827 · Cited by 341 · see citing works
Leist, M., Gantner, F., Jilg, S., & Wendel, A. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.3.1307 · Cited by 332 · see citing works
Self-citationShimizu, S., Eguchi, Y., Kamiike, W., et al. (1996) · PubMed · Cited by 300 · see citing works
Li, Y., Sharov, V. G., Jiang, N., Zaloga, C., Sabbah, H. N., & Chopp, M. (1995) · Europe PMC (PubMed Central) · Cited by 260 · see citing works
Shimizu, S., Eguchi, Y., Kamiike, W., Waguri, S., Uchiyama, Y., Matsuda, H., & Tsujimoto, Y. (1996) · PubMed · Cited by 254 · see citing works
Leist, M., Gantner, F., Künstle, G., Bohlinger, I., Tiegs, G., Bluethmann, H., & Wendel, A. (1996) · Molecular Medicine · doi:10.1007/bf03402207 · Cited by 126 · see citing works
Self-citationAnnexin V A specific probe for apoptotic cells
Martin, S. J., Reutelingsperger, C. P. M., & Green, D. R. (1996) · Cited by 28 · see citing works
Anel, A., Gamen, S., Álava, M. A., et al. (1996) · International Immunology · doi:10.1093/intimm/8.7.1173 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Apoptosis: A Review of Programmed Cell Death
Elmore, S. (2007) · Toxicologic Pathology · doi:10.1080/01926230701320337 · Cited by 13,853 · 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
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
The mitochondrial permeability transition pore and its role in cell death
CROMPTON, M. (1999) · Biochemical Journal · doi:10.1042/bj3410233 · Cited by 2,432 · see citing works
Lemasters, J. J., Nieminen, A.-L., Qian, T., Trost, L. C., Elmore, S. P., Nishimura, Y., Crowe, R. A., Cascio, W. E., Bradham, C. A., Brenner, D. A., et al. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00112-1 · Cited by 1,387 · see citing works
Block copolymer micelles in nanomedicine applications
Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309 · see citing works
DNA damage and the balance between survival and death in cancer biology
Roos, W. P., Thomas, A. D., & Kaina, B. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.2 · Cited by 1,189 · see citing works
Bossy‐Wetzel, E., Newmeyer, D. D., & Green, D. R. (1998) · The EMBO Journal · doi:10.1093/emboj/17.1.37 · Cited by 1,225 · see citing works
Cell death by necrosis: towards a molecular definition
Golstein, P., & Kroemer, G. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.11.001 · Cited by 1,044 · see citing works
Essential versus accessory aspects of cell death: recommendations of the NCCD 2015
Galluzzi, L., Bravo-San Pedro, J. M., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Alnemri, E. S., Altucci, L., Andrews, D., Annicchiarico-Petruzzelli, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.137 · Cited by 1,002 · see citing works
Cell death modalities: classification and pathophysiological implications
Galluzzi, L., Maiuri, M. C., Vitale, I., Zischka, H., Castedo, M., Zitvogel, L., & Kroemer, G. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402148 · Cited by 832 · see citing works
Schinzel, A. C., Takeuchi, O., Huang, Z., Fisher, J. K., Zhou, Z., Rubens, J., Hetz, C., Danial, N. N., Moskowitz, M. A., & Korsmeyer, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505294102 · Cited by 820 · see citing works
Role of mitochondria in oxidative stress and ageing
Lenaz, G. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00120-0 · Cited by 650 · see citing works
Alcohol and mitochondria: a dysfunctional relationship
Hoek, J. B., Cahill, A., & Pastorino, J. G. (2002) · Gastroenterology · doi:10.1053/gast.2002.33613 · Cited by 553 · see citing works
Bernstein, C. (2002) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(02)00009-1 · Cited by 527 · see citing works
Peroxynitrite-induced cytotoxicity: mechanism and opportunities for intervention
Virág, L., Szabó, É., Gergely, P., & Szabó, C. (2003) · Toxicology Letters · doi:10.1016/s0378-4274(02)00508-8 · Cited by 460 · see citing works
Genestier, A.-L., Michallet, M.-C., Prévost, G., Bellot, G., Chalabreysse, L., Peyrol, S., Thivolet, F., Etienne, J., Lina, G., Vallette, F. M., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22684 · Cited by 416 · see citing works
Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling
Gorman, A. M. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00402.x · Cited by 362 · see citing works
Bonora, M., Wieckowski, M. R., Chinopoulos, C., Kepp, O., Kroemer, G., Galluzzi, L., & Pinton, P. (2015) · Oncogene · doi:10.1038/onc.2014.96 · Cited by 330 · see citing works
Yang, H., Rivera, Z., Jube, S., Nasu, M., Bertino, P., Goparaju, C., Franzoso, G., Lotze, M. T., Krausz, T., Pass, H. I., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006542107 · Cited by 281 · see citing works
Central role of mitochondria in drug-induced liver injury
Pessayre, D., Fromenty, B., Berson, A., Robin, M.-A., Lettéron, P., Moreau, R., & Mansouri, A. (2012) · Drug Metabolism Reviews · doi:10.3109/03602532.2011.604086 · Cited by 277 · see citing works
Molecular mechanisms of regulated necrosis
Galluzzi, L., Kepp, O., Krautwald, S., Kroemer, G., & Linkermann, A. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.02.006 · Cited by 258 · 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
Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes
Cantó, C., Sauve, A. A., & Bai, P. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.004 · Cited by 246 · see citing works
Oxidative Stress Causes Heart Failure with Impaired Mitochondrial Respiration
Nojiri, H., Shimizu, T., Funakoshi, M., Yamaguchi, O., Zhou, H., Kawakami, S., Ohta, Y., Sami, M., Tachibana, T., Ishikawa, H., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602118200 · Cited by 230 · see citing works
Goetzman, E. S., & Prochownik, E. V. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00129 · Cited by 199 · see citing works
Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle
Dirks, A. J., Hofer, T., Marzetti, E., Pahor, M., & Leeuwenburgh, C. (2006) · Ageing Research Reviews · doi:10.1016/j.arr.2006.03.002 · Cited by 169 · see citing works
Sörensen, L., Ekstrand, M., Silva, J., Lindqvist, E., Xu, B., Rustin, P., Olson, L., & Larsson, N.-G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08082.2001 · Cited by 167 · see citing works
Abnormal T cell signal transduction in systemic lupus erythematosus
Kammer, G. M., Perl, A., Richardson, B. C., & Tsokos, G. C. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10192 · Cited by 139 · see citing works
Chokshi, N. K., Guner, Y. S., Hunter, C. J., Upperman, J. S., Grishin, A., & Ford, H. R. (2008) · Seminars in Perinatology · doi:10.1053/j.semperi.2008.01.002 · Cited by 137 · see citing works
Elsässer, A., Suzuki, K., & Schaper, J. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1125 · Cited by 138 · see citing works
Wang, X., Ryter, S. W., Dai, C., Tang, Z.-L., Watkins, S. C., Yin, X.-M., Song, R., & Choi, A. M. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301624200 · Cited by 136 · see citing works
Nitric Oxide-Dependent Mitochondrial Biogenesis Generates Ca2+ Signaling Profile of Lupus T Cells
Nagy, G., Barcza, M., Gonchoroff, N., Phillips, P. E., & Perl, A. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3676 · Cited by 132 · see citing works
Anticancer Drugs Targeting the Mitochondrial Electron Transport Chain
Rohlena, J., Dong, L.-F., Ralph, S. J., & Neuzil, J. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.3990 · Cited by 91 · see citing works
NO-Rich Diet for Lifestyle-Related Diseases
Kobayashi, J., Ohtake, K., & Uchida, H. (2015) · Nutrients · doi:10.3390/nu7064911 · Cited by 94 · see citing works
Calcium channelopathies and Alzheimer's disease: Insight into therapeutic success and failures
Chakroborty, S., & Stutzmann, G. E. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.11.012 · Cited by 91 · see citing works
Yoon, Y.-S., Byun, H.-O., Cho, H., Kim, B.-K., & Yoon, G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308489200 · Cited by 91 · see citing works
An Overview of Pathways of Regulated Necrosis in Acute Kidney Injury
Kers, J., Leemans, J. C., & Linkermann, A. (2016) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.03.002 · Cited by 80 · see citing works
Apoptosis in myocardial infarction
Rodríguez, M., Lucchesi, B. R., & Schaper, J. (2002) · Annals of Medicine · doi:10.1080/078538902321012414 · Cited by 81 · see citing works
Zhong, J. L., Yiakouvaki, A., Holley, P., Tyrrell, R. M., & Pourzand, C. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.23419.x · Cited by 68 · see citing works
Loss of autophagy promotes murine acetaminophen hepatotoxicity
Igusa, Y., Yamashina, S., Izumi, K., Inami, Y., Fukada, H., Komatsu, M., Tanaka, K., Ikejima, K., & Watanabe, S. (2012) · Journal of Gastroenterology · doi:10.1007/s00535-011-0500-0 · Cited by 66 · see citing works
Andrés, M. T., Acosta-Zaldívar, M., & Fierro, J. F. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03130-15 · Cited by 41 · see citing works
Escobar, S. J. D. M., Fong, G. M., Winnischofer, S. M. B., Simone, M., Munoz, L., Dennis, J. M., Rocha, M. E. M., & Witting, P. K. (2019) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2018.11.022 · Cited by 33 · see citing works
- Authors
- Leist, M., Single, B., Castoldi, A. F., Kühnle, S., & Nicotera, P.
- Affiliations
- University of Konstanz (DE)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1997-04-21
- Volume
- 185
- Issue
- 8
- Pages
- 1481-1486
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2196283
- OpenAlex
- W2135325091
- Cited by
- 1,871
- References
- 30
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 25 · 2023: 27 · 2022: 30 · 2021: 35 · 2020: 51 · 2019: 32 · 2018: 49 · 2017: 54 · 2016: 47 · 2015: 54 · 2014: 51 · 2013: 55 · 2012: 89
- FWCI
- 30.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- KOPS (University of Konstanz) (submittedVersion)
- Funders
- European Science Foundation
- Universität Konstanz
- 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
- adenosine triphosphate, apoptosis, necrosis, cell death, human T cells, staurosporine, Fas, glucose, glycolysis, mitochondrial ATP production, nuclear condensation, DNA fragmentation, ATP depletion
- MeSH terms
- Adenosine Triphosphate, Cell Line, Cell Nucleus, Cysteine Endopeptidases, Humans, Mitochondria, Necrosis, Nuclear Proteins, Cell Death, Apoptosis, Lamins
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
