Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features
Abstract
Necroptosis, necrosis and secondary necrosis following apoptosis represent different modes of cell death that eventually result in similar cellular morphology including rounding of the cell, cytoplasmic swelling, rupture of the plasma membrane and spilling of the intracellular content. Subcellular events during tumor necrosis factor (TNF)-induced necroptosis, H(2)O(2)-induced necrosis and anti-Fas-induced secondary necrosis were studied using high-resolution time-lapse microscopy. The cellular disintegration phase of the three types of necrosis is characterized by an identical sequence of subcellular events, including oxidative burst, mitochondrial membrane hyperpolarization, lysosomal membrane permeabilization and plasma membrane permeabilization, although with different kinetics. H(2)O(2)-induced necrosis starts immediately by lysosomal permeabilization. In contrast, during TNF-mediated necroptosis and anti-Fas-induced secondary necrosis, this is a late event preceded by a defined signaling phase. TNF-induced necroptosis depends on receptor-interacting protein-1 kinase, mitochondrial complex I and cytosolic phospholipase A(2) activities, whereas H(2)O(2)-induced necrosis requires iron-dependent Fenton reactions.
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There is abundant evidence that iron can cause apoptosis.
“there is abundant evidence for the ability of iron to cause apoptosis (Kotamraju et al. 2004a, b; Kurz et al. 2007, 2008b; Vanden Berghe et al. 2009)”
From Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples (2010) · cites this paper as Vanden Berghe et al. 2009
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Cites
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009
Kroemer, G., Galluzzi, L., Vandenabeele, P., Abrams, J., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., El-Deiry, W. S., Golstein, P., Green, D. R., et al. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.150 · Cited by 3,399 · see citing works
Self-citationChemical 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 · see citing works
Kazama, H., Ricci, J.-E., Herndon, J. M., Hoppe, G., Green, D. R., & Ferguson, T. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.013 · Cited by 627 · see citing works
KURZ, T., LEAKE, A., von ZGLINICKI, T., & BRUNK, U. T. (2004) · Biochemical Journal · doi:10.1042/bj20031029 · Cited by 101 · see citing works
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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695 · see citing works
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
Self-citationMolecular 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
Self-citationRegulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735 · see citing works
Self-citationLysosomes as dynamic regulators of cell and organismal homeostasis
Ballabio, A., & Bonifacino, J. S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0185-4 · Cited by 1,469 · see citing works
Rogers, C., Fernandes-Alnemri, T., Mayes, L., Alnemri, D., Cingolani, G., & Alnemri, E. S. (2017) · Nature Communications · doi:10.1038/ncomms14128 · Cited by 1,510 · see citing works
“Intriguingly, a process called secondary necrosis has been observed following activation of the apoptotic programme in many cell types 16,34 .”
InfluentialNecroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance
Kaczmarek, A., Vandenabeele, P., & Krysko, D. V. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.003 · Cited by 1,411 · see citing works
Self-citationPyroptosis versus necroptosis: similarities, differences, and crosstalk
Frank, D., & Vince, J. E. (2019) · Cell Death & Differentiation · doi:10.1038/s41418-018-0212-6 · Cited by 1,062 · 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
Self-citationTNF and ROS crosstalk in inflammation
Blaser, H., Dostert, C., Mak, T. W., & Brenner, D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.12.002 · Cited by 1,008 · see citing works
Lysosomal cell death at a glance
Aits, S., & Jäättelä, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.091181 · Cited by 667 · see citing works
Eckhart, L., Lippens, S., Tschachler, E., & Declercq, W. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.010 · Cited by 515 · see citing works
Self-citationApoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium
Günther, C., Neumann, H., Neurath, M. F., & Becker, C. (2013) · Gut · doi:10.1136/gutjnl-2011-301364 · Cited by 462 · see citing works
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
Kell, D. B. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0577-x · Cited by 361 · see citing works
Widespread Mitochondrial Depletion via Mitophagy Does Not Compromise Necroptosis
Tait, S. W. G., Oberst, A., Quarato, G., Milasta, S., Haller, M., Wang, R., Karvela, M., Ichim, G., Yatim, N., Albert, M. L., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.034 · Cited by 303 · see citing works
Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production
Fortes, G. B., Alves, L. S., de Oliveira, R., Dutra, F. F., Rodrigues, D., Fernandez, P. L., Souto-Padron, T., De Rosa, M. J., Kelliher, M., Golenbock, D., et al. (2012) · Blood · doi:10.1182/blood-2011-08-375303 · Cited by 246 · see citing works
Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors
Canli, Ö., Alankuş, Y. B., Grootjans, S., Vegi, N., Hültner, L., Hoppe, P. S., Schroeder, T., Vandenabeele, P., Bornkamm, G. W., & Greten, F. R. (2016) · Blood · doi:10.1182/blood-2015-06-654194 · Cited by 247 · see citing works
Self-citationXia, B., Fang, S., Chen, X., Hu, H., Chen, P., Wang, H., & Gao, Z. (2016) · Cell Research · doi:10.1038/cr.2016.26 · Cited by 202 · see citing works
Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury
Sancho-Martínez, S. M., López-Novoa, J. M., & López-Hernández, F. J. (2015) · Clinical Kidney Journal · doi:10.1093/ckj/sfv069 · Cited by 130 · see citing works
‘Hints’ in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death
Qiu, S., Liu, J., & Xing, F. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.24 · Cited by 111 · see citing works
Identification of Small Molecule Inhibitors of Phosphatidylinositol 3-Kinase and Autophagy
Farkas, T., Daugaard, M., & Jäättelä, M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.269134 · Cited by 91 · see citing works
Location, location, location: A compartmentalized view of TNF-induced necroptotic signaling.
Samson, A. L., Garnish, S. E., Hildebrand, J. M., & Murphy, J. M. (2021) · Science Signaling · doi:10.1126/scisignal.abc6178 · Cited by 82 · see citing works
Brojatsch, J., Lima, H., Palliser, D., Jacobson, L. S., Muehlbauer, S. M., Furtado, R., Goldman, D. L., Lisanti, M. P., & Chandran, K. (2015) · Cell Cycle · doi:10.4161/15384101.2014.991194 · Cited by 50 · see citing works
Bencze, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010362 · Cited by 20 · see citing works
- Authors
- Berghe, T. V., Vanlangenakker, N., Parthoens, E., Deckers, W., Devos, M., Festjens, N., Guerin, C. J., Brunk, U. T., Declercq, W., & Vandenabeele, P.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- Linköping University (SE)
- Corresponding author
- Vandenabeele, P
- Venue
- Cell Death & Differentiation
- Published
- 2009-12-11
- Volume
- 17
- Issue
- 6
- Pages
- 922-930
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W2085006338
- Cited by
- 639
- References
- 4
- Citations by year
- 2026: 16 · 2025: 27 · 2024: 55 · 2023: 43 · 2022: 44 · 2021: 59 · 2020: 44 · 2019: 35 · 2018: 35 · 2017: 40 · 2016: 31 · 2015: 41 · 2014: 48 · 2013: 45 · 2012: 36
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- European Commission (200767)
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Vlaams Instituut voor Biotechnologie
- Vlaamse regering
- Bijzonder Onderzoeksfonds UGent
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Social Sciences › Anthropology › Death, Funerary Practices, and Mourning
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- necroptosis, necrosis, secondary necrosis, lysosomal membrane permeabilization, plasma membrane permeabilization, mitochondrial membrane hyperpolarization, RIP1 kinase, mitochondrial complex I, cytosolic phospholipase A2, Fenton reaction, iron, respiratory burst, cell death signaling
- MeSH terms
- Animals, Cell Membrane Permeability, Hydrogen Peroxide, Iron, Lysosomes, Necrosis, Tumor Necrosis Factor-alpha, Reactive Oxygen Species, Electron Transport Complex I, Cell Line, Tumor, Mice, Membrane Potential, Mitochondrial, Receptor-Interacting Protein Serine-Threonine Kinases, Phospholipases A2, Cytosolic
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