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Cell death: a review of the major forms of apoptosis, necrosis and autophagy
Abstract
Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme‐dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.
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Cites
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 15,725
Apoptosis: A Review of Programmed Cell Death
Elmore, S. (2007) · Toxicologic Pathology · doi:10.1080/01926230701320337 · Cited by 13,853
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., Belli, B. A., Bruncko, M., Deckwerth, T. L., Dinges, J., Hajduk, P. J., et al. (2005) · Nature · doi:10.1038/nature03579 · Cited by 3,416
Apoptosis, oncosis, and necrosis. An overview of cell death.
Majno, G., & Joris, I. (1995) · PubMed · Cited by 3,306
Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
Wang, Y., Gao, W., Shi, X., Ding, J., Liu, W., He, H., Wang, K., & Shao, F. (2017) · Nature · doi:10.1038/nature22393 · Cited by 3,199
Pyroptosis: host cell death and inflammation
Bergsbaken, T., Fink, S. L., & Cookson, B. T. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2070 · Cited by 3,183
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068
Autophagy in Health and Disease: A Double-Edged Sword
Shintani, T., & Klionsky, D. J. (2004) · Science · doi:10.1126/science.1099993 · Cited by 2,534
Non-canonical inflammasome activation targets caspase-11
Kayagaki, N., Warming, S., Lamkanfi, M., Walle, L. V., Louie, S., Dong, J., Newton, K., Qu, Y., Liu, J., Heldens, S., et al. (2011) · Nature · doi:10.1038/nature10558 · Cited by 2,530
Apoptosis, Pyroptosis, and Necrosis: Mechanistic Description of Dead and Dying Eukaryotic Cells
Fink, S. L., & Cookson, B. T. (2005) · Infection and Immunity · doi:10.1128/iai.73.4.1907-1916.2005 · Cited by 2,205
Death and anti-death: tumour resistance to apoptosis
Igney, F. H., & Krammer, P. H. (2002) · Nature Reviews Cancer · doi:10.1038/nrc776 · Cited by 2,075
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.-L., Schneider, P., Seed, B., & Tschopp, J. (2000) · Nature Immunology · doi:10.1038/82732 · Cited by 1,938
Mathew, R., Karantza-Wadsworth, V., & White, E. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2254 · Cited by 1,798
Wang, H., Sun, L., Su, L., Rizo, J., Liu, L., Wang, L.-F., Wang, F.-S., & Wang, X. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.003 · Cited by 1,563
Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., Salfeld, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90490-5 · Cited by 1,417
Death by design: apoptosis, necrosis and autophagy
Edinger, A. L., & Thompson, C. B. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.09.011 · Cited by 1,364
Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
Miao, E. A., Leaf, I. A., Treuting, P. M., Mao, D. P., Dors, M., Sarkar, A., Warren, S. E., Wewers, M. D., & Aderem, A. (2010) · Nature Immunology · doi:10.1038/ni.1960 · Cited by 1,336
Varfolomeev, E. E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J. S., Mett, I. L., Rebrikov, D., Brodianski, V. M., Kemper, O. C., Kollet, O., et al. (1998) · Immunity · doi:10.1016/s1074-7613(00)80609-3 · Cited by 1,234
Apoptotic cell clearance: basic biology and therapeutic potential
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3607 · Cited by 1,223
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222
The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
Murphy, J. M., Czabotar, P. E., Hildebrand, J. M., Lucet, I. S., Zhang, J.-G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N., Metcalf, D., Webb, A. I., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.018 · Cited by 1,220
Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis
Spencer, S. L., Gaudet, S., Albeck, J. G., Burke, J. M., & Sorger, P. K. (2009) · Nature · doi:10.1038/nature08012 · Cited by 1,021
Three-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 911
Unveiling the roles of autophagy in innate and adaptive immunity
Levine, B., & Deretic, V. (2007) · Nature Reviews Immunology · doi:10.1038/nri2161 · Cited by 906
Hypoxia-induced neutrophil survival is mediated by HIF-1α–dependent NF-κB activity
Walmsley, S. R., Print, C., Farahi, N., Peyssonnaux, C., Johnson, R. S., Cramer, T., Sobolewski, A., Condliffe, A. M., Cowburn, A. S., Johnson, N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040624 · Cited by 891
Roberts, A. W., Seymour, J. F., Brown, J. R., Wierda, W. G., Kipps, T. J., Khaw, S. L., Carney, D. A., He, S. Z., Huang, D. C. S., Xiong, H., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.34.7898 · Cited by 830
The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1
Hersh, D., Monack, D. M., Smith, M. R., Ghori, N., Falkow, S., & Zychlinsky, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2396 · Cited by 788
Microautophagy: lesser-known self-eating
Li, W.-W., Li, J., & Bao, J.-K. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0865-5 · Cited by 738
Apoptosis, autophagy, and more
Lockshin, R. A., & Zakeri, Z. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.04.011 · Cited by 700
Apoptosis and Necrosis in the Liver: A Tale of Two Deaths?
Malhi, H., Gores, G. J., & Lemasters, J. J. (2006) · Hepatology · doi:10.1002/hep.21062 · Cited by 691
Apaf-1 and Caspase-9 in p53-Dependent Apoptosis and Tumor Inhibition
Soengas, M. S., Alarcón, R. M., Yoshida, H., J., A., Giaccia, Hakem, R., Mak, T. W., & Lowe, S. W. (1999) · Science · doi:10.1126/science.284.5411.156 · Cited by 660
Autophagy failure in Alzheimer's disease—locating the primary defect
Nixon, R. A., & Yang, D.-S. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.021 · Cited by 595
Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury
Jaeschke, H., & Lemasters, J. J. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)01209-5 · Cited by 589
Dice, J. F. (2007) · Autophagy · doi:10.4161/auto.4144 · Cited by 569
Clearance of apoptotic cells: implications in health and disease
Elliott, M. R., & Ravichandran, K. S. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201004096 · Cited by 551
RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis
Dannappel, M., Vlantis, K., Kumari, S., Polykratis, A., Kim, C., Wachsmuth, L., Eftychi, C., Lin, J., Corona, T., Hermance, N., et al. (2014) · Nature · doi:10.1038/nature13608 · Cited by 534
Autophagy: Many paths to the same end
Cuervo, A. M. (2004) · Molecular and Cellular Biochemistry · doi:10.1023/b:mcbi.0000041848.57020.57 · Cited by 476
Interactions of Tumor Necrosis Factor (TNF) and TNF Receptor Family Members in the Mouse and Human
Bossen, C., Ingold, K., Tardivel, A., Bodmer, J.-L., Gaide, O., Hertig, S., Ambrose, C., Tschopp, J., & Schneider, P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601553200 · Cited by 443
The Apaf-1 apoptosome: a large caspase-activating complex
Cain, K., Bratton, S. B., & Cohen, G. M. (2002) · Biochimie · doi:10.1016/s0300-9084(02)01376-7 · Cited by 439
Mitochondrial cell death effectors
Brenner, D., & Mak, T. W. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.09.004 · Cited by 416
Granzyme A Induces Caspase-Independent Mitochondrial Damage, a Required First Step for Apoptosis
Martinvalet, D., Zhu, P., & Lieberman, J. (2005) · Immunity · doi:10.1016/j.immuni.2005.02.004 · Cited by 408
Necroptosis microenvironment directs lineage commitment in liver cancer
Seehawer, M., Heinzmann, F., D’Artista, L., Harbig, J., Roux, P.-F., Hoenicke, L., Dang, H., Klotz, S., Robinson, L., Doré, G., et al. (2018) · Nature · doi:10.1038/s41586-018-0519-y · Cited by 406
Apoptosis in Parkinson's disease: Signals for neuronal degradation
Tatton, W. G., Chalmers-Redman, R., Brown, D., & Tatton, N. (2003) · Annals of Neurology · doi:10.1002/ana.10489 · Cited by 397
Lemasters, J. J. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.1.g1 · Cited by 383
Localization of Apoptotic Macrophages at the Site of Plaque Rupture in Sudden Coronary Death
Kolodgie, F. D., Narula, J., Burke, A. P., Haider, N., Farb, A., Hui-Liang, Y., Smialek, J., & Virmani, R. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64641-x · Cited by 366
Shikonin circumvents cancer drug resistance by induction of a necroptotic death
Han, W., Li, L., Qiu, S., Lu, Q., Pan, Q., Gu, Y., Luo, J., & Hu, X. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0511 · Cited by 364
Sica, A., Wang, J. M., Colotta, F., Dejana, E., Mantovani, A., Oppenheim, J. J., Larsen, C. G., Zachariae, C. O. C., & Matsushima, K. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.8.3034 · Cited by 342
Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection
Aachoui, Y., Sagulenko, V., Miao, E. A., & Stacey, K. J. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.04.004 · Cited by 296
Bonnet, M. C., Preukschat, D., Welz, P.-S., van Loo, G., Ermolaeva, M. A., Bloch, W., Haase, I., & Pasparakis, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.014 · Cited by 295
Moriwaki, K., Bertin, J., Gough, P. J., Orlowski, G. M., & Chan, F. K. (2015) · Cell Death & Disease · doi:10.1038/cddis.2015.16 · Cited by 247
Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer
Wang, Z., Li, S., Cao, Y., Tian, X., Zeng, R., Liao, D.-F., & Cao, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/9875298 · Cited by 219
Programmed Cell Death of Developing Mammalian Neurons after Genetic Deletion of Caspases
Oppenheim, R. W., Flavell, R. A., Vinsant, S., Prevette, D., Kuan, C.-Y., & Rakic, P. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04752.2001 · Cited by 216
Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
Dickson, D. W. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422317 · Cited by 201
Salmonella-induced cell death: apoptosis, necrosis or programmed cell death?
Boise, L. H., & Collins, C. M. (2001) · Trends in Microbiology · doi:10.1016/s0966-842x(00)01937-5 · Cited by 180
Liu, X.-H., Kwon, D., Schielke, G. P., Yang, G.-Y., Silverstein, F. S., & Barks, J. D. E. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199910000-00006 · Cited by 168
Caspases and cancer: mechanisms of inactivation and new treatment modalities.
Philchenkov, A., Zavelevich, M. P., Kroczak, T., & Łoś, M. (2004) · PubMed · Cited by 163
SHAO, S., Su, L., Qin, Y., Wang, X., Yang, Y., Bai, H., Zhou, L., Zhao, C., & Wang, C. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2313 · Cited by 161
Protective Roles for Caspase-8 and cFLIP in Adult Homeostasis
Weinlich, R., Oberst, A., Dillon, C. P., Janke, L. J., Milasta, S., Lukens, J. R., Rodriguez, D. A., Gurung, P., Savage, C., Kanneganti, T. D., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.045 · Cited by 157
The mitochondrial death squad: hardened killers or innocent bystanders?
Ekert, P. G., & Vaux, D. L. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.001 · Cited by 123
Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets
Lancelot, J., Caby, S., Dubois, F., Vanderstraete, M., Trolet, J., Oliveira, G., Bracher, F., Jung, M., & Pierce, R. J. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002428 · Cited by 96
Loss of Caspase-9 Provides Genetic Evidence for the Type I/II Concept of CD95-mediated Apoptosis
Samraj, A. K., Keil, E., Ueffing, N., Schulze‐Osthoff, K., & Schmitz, I. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603487200 · Cited by 84
Autophagy- An emerging target for melanoma therapy
Ndoye, A., & Weeraratna, A. T. (2016) · F1000Research · doi:10.12688/f1000research.8347.1 · Cited by 73
Cell death/apoptosis: normal, chemically induced, and teratogenic effect
Zakeri, Z., & Ahuja, H. S. (1997) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(97)00181-4 · Cited by 67
Tissue transglutaminase: a new target to reverse cancer drug resistance
Budillon, A., Carbone, C., & Gennaro, E. D. (2011) · Amino Acids · doi:10.1007/s00726-011-1167-9 · Cited by 60
Fas‐induced apoptosis, and diseases caused by its abnormality
Nagata, S. (1996) · Genes to Cells · doi:10.1046/j.1365-2443.1996.d01-214.x · Cited by 58
Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME
Zhang, X., & Zhang, H. (2018) · Science China Life Sciences · doi:10.1007/s11427-017-9158-x · Cited by 45
Mechanism and disease implications of necroptosis and neuronal inflammation
Oliveira, S. R., Amaral, J. D., & Rodrigues, C. M. P. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0872-7 · Cited by 26
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Metadata
- Authors
- D’Arcy, M. S.
- Venue
- Cell Biology International
- Publisher
- Wiley
- Published
- 2019-04-25
- Volume
- 43
- Issue
- 6
- Pages
- 582-592
- ISSN
- 1065-6995 (ISSN-L)
- 1095-8355
- OpenAlex
- W2937346106
- Cited by
- 2,307
- References
- 68
- FWCI
- 68.61
- Type
- journal article
- Language
- en
- Open access
- closed
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