Other forms of cell death
Here we describe the other forms of cell death that can occur.
Download our guide on cell death analysis types
Parthanatos
Parthanatos is a non-apoptotic form of cell death that has been implicated in a range of diseases, including Parkinson’s disease, diabetes and stroke. Parthanatos initiation involves over-activation of the nuclear protein PARP1 (poly[ADP-ribose] polymerase 1)24, which under physiological conditions, is involved in a variety of cellular process including DNA repair and transcription25. Ultimately parthanatos results in loss of cell membrane integrity.
Over activation of PARP1 is stimulated by DNA damage and ROS. When excessively activated, PARP1 uses NAD+ to generate polymers of PAR. The generation of PAR polymers results in transferal of apoptosis inducing factor (AIF) from mitochondria to the nucleus24. The pathway for parthanatos is incompletely understood; parthanatos may cause cell death through depletion of cellular NAD+ or AIF release, but at present the executioner mechanism has not been confirmed.
NETosis
NETosis is a pathogen-induced cell death mechanism in neutrophils, characterized by the release of neutrophil extracellular traps (NETs); chromatin structures that contain proteins capable of trapping exogenous bacteria and other pathogens.
NETosis occurs following PMA activation of protein kinase C and the raf-mitogenactivated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway.
Anoikis
Anoikis is a form of programmed cell death related to apoptosis. It is induced by cell detachment from the extracellular matrix. Under conditions where cells are attached to the extracellular matrix, anoikis is prevented by pro-survival signaling initiated by integrins – mediators of cell-ECM interactions.
Upon detachment, proapoptotic proteins Bid and Bim accumulate and drive apoptosis via the intrinsic pathway26. Alternatively, ECM detachment can release the mitochondrial Bit1 protein into the cytoplasm, which triggers apoptosis via a caspase-independent mechanism27.
Loss of anoikis ability is a key step in cancer development. Research is currently underway to understand how cancer cells are able to evade anoikis.
For more information on apoptosis, see our apoptosis ebook.
Entosis
Cell death by entosis involves one cell invading into another. Like anoikis, this form of cell death occurs in response to cell detachment from the ECM. Entosis is triggered by adherens junction formation in the absence of integrin-ECM attachment. During entosis, cell invasion involves Rho GTPase and its downstream effector ROCK28.
References
24. Fatokun, A. A., Dawson, V. L. & Dawson, T. M. Parthanatos: Mitochondrial-linked mechanisms and therapeutic opportunities. Br. J. Pharmacol. 171, 2000–2016 (2014).
25. Krietsch, J. et al. Reprogramming cellular events by poly(ADP-ribose)-binding proteins. Mol. Aspects Med. 34, 1066–1087 (2013).
26. Paoli, P., Giannoni, E. & Chiarugi, P. Anoikis molecular pathways and its role in cancer progression. Biochim. Biophys. Acta 1833, 3481–98 (2013).
27. Jan, Y. et al. A Mitochondrial Protein, Bit1, Mediates Apoptosis Regulated by Integrins and Groucho/TLE Corepressors. Cell 116, 751–762 (2004).
28. Vanden Berghe, T. et al. Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods 61, 117–129 (2013).