Skip to main content
SpringerLink
Log in

Apoptotic Features in Non-Apoptotic Processes

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Apoptosis is the most thoroughly studied type of regulated cell death. Certain events, such as externalization of phosphatidylserine (PS) into the outer leaflet of plasma membrane, mitochondrial outer membrane permeabilization, caspase cascade activation, DNA fragmentation and blebbing, are widely considered to be hallmarks of apoptosis as well as being traditionally viewed as irreversible. This review shows that under particular circumstances these events can also participate in physiological processes not associated with initiation of apoptosis, such as cell differentiation, division, and motility, as well as non-apoptotic types of cell death. Moreover, these events may often be reversible. This review focuses on three processes: phosphatidylserine externalization, blebbing, and activation of apoptotic caspases. Mitochondrial outer membrane permeabilization and DNA fragmentation are not discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IL:

interleukin

MOMP:

mitochondrial outer membrane permeabilization

PS:

phosphatidylserine

References

  1. Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., et al. (2018) Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death, Cell Death Differ., 25, 486-541, https://doi.org/10.1038/s41418-017-0012-4.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Saraste, A., and Pulkki, K. (2000) Morphologic and biochemical hallmarks of apoptosis, Cardiovasc. Res., 45, 528-537, https://doi.org/10.1016/s0008-6363(99)00384-3.

    Article  CAS  PubMed  Google Scholar 

  3. Zakharov, I. I., Savitskaya, M. A., and Onishchenko, G. E. (2020) The problem of apoptotic processes reversibility, Biochemistry (Moscow), 85, 1145-1158, https://doi.org/10.1134/S000629792010003X.

    Article  CAS  Google Scholar 

  4. Whitlock, J. M., and Chernomordik, L. V. (2021) Flagging fusion: Phosphatidylserine signaling in cell-cell fusion, J. Biol. Chem., 296, 100411, https://doi.org/10.1016/j.jbc.2021.100411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fadok, V. A., Voelker, D. R., Campbell, P. A., Cohen, J. J., Bratton, D. L., et al. (1992) Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages, J. Immunol., 148, 2207-2216.

    CAS  PubMed  Google Scholar 

  6. Segawa, K., and Nagata, S. (2015) An apoptotic “eat me” signal: Phosphatidylserine exposure, Trends Cell Biol., 25, 639-650, https://doi.org/10.1016/j.tcb.2015.08.003.

    Article  CAS  PubMed  Google Scholar 

  7. Sessions, A., and Horwitz, A. F. (1981) Myoblast aminophospholipid asymmetry differs from that of fibroblasts, FEBS Lett., 134, 75-78, https://doi.org/10.1016/0014-5793(81)80554-6.

    Article  CAS  PubMed  Google Scholar 

  8. Van den Eijnde, S.M., van den Hoff, M. J., Reutelingsperger, C. P., van Heerde, W. L., Henfling, M. E., et al. (2001) Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation, J. Cell Sci., 114 (Pt. 20), 3631-3642.

    Article  Google Scholar 

  9. Ehlen, H. W., Chinenkova, M., Moser, M., Munter, H. M., Krause, Y., et al. (2013) Inactivation of anoctamin-6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues, J. Bone Miner. Res., 28, 246-259, https://doi.org/10.1002/jbmr.1751.

    Article  CAS  PubMed  Google Scholar 

  10. Curia, C. A., Ernesto, J. I., Stein, P., Busso, D., Schultz, R. M., et al. (2013) Fertilization induces a transient exposure of phosphatidylserine in mouse eggs, PLoS One, 8, e71995, https://doi.org/10.1371/journal.pone.0071995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zwaal, R. F., Bevers, E. M., Comfurius, P., Rosing, J., Tilly, R. H., et al. (1989) Loss of membrane phospholipid asymmetry during activation of blood platelets and sickled red cells; mechanisms and physiological significance, Mol. Cell. Biochem., 91, 23-31, https://doi.org/10.1007/BF00228075.

    Article  CAS  PubMed  Google Scholar 

  12. Boyle, E. M., Pohlman, T. H., Cornejo, C. J., and Verrier, E. D. (1996) Endothelial cell injury in cardiovascular surgery: Ischemia-reperfusion, Ann. Thor. Surg., 62, 1868-1875, https://doi.org/10.1016/s0003-4975(96)00950-2.

    Article  Google Scholar 

  13. Park, M., and Kang, K. W. (2019) Phosphatidylserine receptor-targeting therapies for the treatment of cancer, Arch. Pharm. Res., 42, 617-628, https://doi.org/10.1007/s12272-019-01167-4.

    Article  CAS  PubMed  Google Scholar 

  14. Riedl, S., Rinner, B., Asslaber, M., Schaider, H., Walzer, S., et al. (2011) In search of a novel target – phosphatidylserine exposed by non-apoptotic tumor cells and metastases of malignancies with poor treatment efficacy, Biochim. Biophys. Acta, 1808, 2638-2645, https://doi.org/10.1016/j.bbamem.2011.07.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vogt, E., Ng, A. K., and Rote, N. S. (1996) A model for the antiphospholipid antibody syndrome: Monoclonal antiphosphatidylserine antibody induces intrauterine growth restriction in mice, Am. J. Obstet. Gynecol., 174, 700-777, https://doi.org/10.1016/s0002-9378(96)70453-2.

    Article  CAS  PubMed  Google Scholar 

  16. Gong, Y. N., Crawford, J. C., Heckmann, B. L., and Green, D. R. (2019) To the edge of cell death and back, FEBS J., 286, 430-440, https://doi.org/10.1111/febs.14714.

    Article  CAS  PubMed  Google Scholar 

  17. Segawa, K., Suzuki, J., and Nagata, S. (2014) Flippases and scramblases in the plasma membrane, Cell Cycle, 13, 2990-2991, https://doi.org/10.4161/15384101.2014.962865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Damek-Poprawa, M., Golub, E., Otis, L., Harrison, G., Phillips, C., et al. (2006) Chondrocytes utilize a cholesterol-dependent lipid translocator to externalize phosphatidylserine, Biochemistry, 45, 3325-3336, https://doi.org/10.1021/bi0515927.

    Article  CAS  PubMed  Google Scholar 

  19. Segawa, K., Yanagihashi, Y., Yamada, K., Suzuki, C., Uchiyama, Y., et al. (2018) Phospholipid flippases enable precursor B cells to flee engulfment by macrophages, Proc. Natl. Acad. Sci. USA, 115, 12212-12217, https://doi.org/10.1073/pnas.1814323115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tsuchiya, M., Hara, Y., Okuda, M., Itoh, K., Nishioka, R., et al. (2018) Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation, Nat. Commun., 9, 2049, https://doi.org/10.1038/s41467-018-04436-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jeong, J., and Conboy, I. M. (2011) Phosphatidylserine directly and positively regulates fusion of myoblasts into myotubes, Biochem. Biophys. Res. Commun., 414, 9-13, https://doi.org/10.1016/j.bbrc.2011.08.128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shin, H.-W., and Takatsu, H. (2020) Phosphatidylserine exposure in living cells, Crit. Rev. Biochem. Mol. Biol., 55, 166-178, https://doi.org/10.1080/10409238.2020.1758624.

    Article  CAS  PubMed  Google Scholar 

  23. Verma, S. K., Leikina, E., Melikov, K., Gebert, C., Kram, V., et al. (2018) Cell-surface phosphatidylserine regulates osteoclast precursor fusion, J. Biol. Chem., 293, 254-270, https://doi.org/10.1074/jbc.M117.809681.

    Article  CAS  PubMed  Google Scholar 

  24. Helming, L., Winter, J., and Gordon, S. (2009) The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion, J. Cell Sci., 122(Pt. 4), 453-459, https://doi.org/10.1242/jcs.037200.

    Article  CAS  Google Scholar 

  25. Lyden, T. W., Ng, A. K., and Rote, N. S. (1993) Modulation of phosphatidylserine epitope expression by BeWo cells during forskolin treatment, Placenta, 14, 177-186, https://doi.org/10.1016/s0143-4004(05)80259-0.

    Article  CAS  PubMed  Google Scholar 

  26. Das, M., Xu, B., Lin, L., Chakrabarti, S., Shivaswamy, V., et al. (2004) Phosphatidylserine efflux and intercellular fusion in a BeWo model of human villous cytotrophoblast, Placenta, 25, 396-407, https://doi.org/10.1016/j.placenta.2003.11.004.

    Article  CAS  PubMed  Google Scholar 

  27. Gadella, B. M., and Harrison, R. A. (2002) Capacitation induces cyclic adenosine 3′,5′-monophosphate-dependent, but apoptosis-unrelated, exposure of aminophospholipids at the apical head plasma membrane of boar sperm cells, Biol. Reprod., 67, 340-350, https://doi.org/10.1095/biolreprod67.1.340.

    Article  CAS  PubMed  Google Scholar 

  28. Clarke, R. J., Hossain, K. R., and Cao, K. (2020) Physiological roles of transverse lipid asymmetry of animal membranes, Biochim. Biophys. Acta, 1862, 183382, https://doi.org/10.1016/j.bbamem.2020.183382.

    Article  CAS  Google Scholar 

  29. Thiagarajan, P., Parker, C. J., and Prchal, J. T. (2021) How do red blood cells die? Front. Physiol., 12, 655393, https://doi.org/10.3389/fphys.2021.655393.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Test, S. T., and Mitsuyoshi, J. (1997) Activation of the alternative pathway of complement by calcium-loaded erythrocytes resulting from loss of membrane phospholipid asymmetry, J. Lab. Clin. Med., 130, 169-182, https://doi.org/10.1016/s0022-2143(97)90093-7.

    Article  CAS  PubMed  Google Scholar 

  31. Zwaal, R. F., Comfurius, P., and Bevers, E. M. (2005) Surface exposure of phosphatidylserine in pathological cells, Cell. Mol. Life Sci., 62, 971-988, https://doi.org/10.1007/s00018-005-4527-3.

    Article  CAS  PubMed  Google Scholar 

  32. Qu, J., Conroy, L. A., Walker, J. H., Wooding, F. B., and Lucy, J. A. (1996) Phosphatidylserine-mediated adhesion of T-cells to endothelial cells, Biochem. J., 317 (Pt. 2), 343-346, https://doi.org/10.1042/bj3170343.

    Article  Google Scholar 

  33. Lupu, F., Moldovan, N., Ryan, J., Stern, D., and Simionescu, N. (1993) Intrinsic procoagulant surface induced by hypercholesterolaemia on rabbit aortic endothelium, Blood Coagul. Fibrinol. Int. J. Haemost. Thromb., 4, 743-752.

    Article  CAS  Google Scholar 

  34. Christiansen, V. J., Sims, P. J., and Hamilton, K. K. (1997) Complement C5b-9 increases plasminogen binding and activation on human endothelial cells, Arterioscler. Thromb. Vasc. Biol., 17, 164-171, https://doi.org/10.1161/01.atv.17.1.164.

    Article  CAS  PubMed  Google Scholar 

  35. Bevers, E. M., Rosing, J., and Zwaal, R. F. (1985) Development of procoagulant binding sites on the platelet surface, Adv. Exp. Med. Biol., 192, 359-371, https://doi.org/10.1007/978-1-4615-9442-0_25.

    Article  CAS  PubMed  Google Scholar 

  36. Martin, S., Pombo, I., Poncet, P., David, B., Arock, M., et al. (2000) Immunologic stimulation of mast cells leads to the reversible exposure of phosphatidylserine in the absence of apoptosis, Int. Arch. Allergy Immunol., 123, 249-258, https://doi.org/10.1159/000024451.

    Article  CAS  PubMed  Google Scholar 

  37. Connor, J., Bucana, C., Fidler, I. J., and Schroit, A. J. (1989) Differentiation-dependent expression of phosphatidylserine in mammalian plasma membranes: quantitative assessment of outer-leaflet lipid by prothrombinase complex formation, Proc. Natl. Acad. Sci. USA, 86, 3184-3188, https://doi.org/10.1073/pnas.86.9.3184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Utsugi, T., Schroit, A. J., Connor, J., Bucana, C. D., and Fidler, I. J. (1991) Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes, Cancer Res., 51, 3062-3066.

    CAS  PubMed  Google Scholar 

  39. Woehlecke, H., Pohl, A., Alder-Baerens, N., Lage, H., and Herrmann, A. (2003) Enhanced exposure of phosphatidylserine in human gastric carcinoma cells overexpressing the half-size ABC transporter BCRP (ABCG2), Biochem. J., 376 (Pt. 2), 489-495, https://doi.org/10.1042/BJ20030886.

    Article  Google Scholar 

  40. Schröder-Borm, H., Bakalova, R., and Andrä, J. (2005) The NK-lysin derived peptide NK-2 preferentially kills cancer cells with increased surface levels of negatively charged phosphatidylserine, FEBS Lett., 579, 6128-6134, https://doi.org/10.1016/j.febslet.2005.09.084.

    Article  CAS  PubMed  Google Scholar 

  41. Comfurius, P., Senden, J. M., Tilly, R. H., Schroit, A. J., Bevers, E. M., et al. (1990) Loss of membrane phospholipid asymmetry in platelets and red cells may be associated with calcium-induced shedding of plasma membrane and inhibition of aminophospholipid translocase, Biochim. Biophys. Acta, 1026, 153-160, https://doi.org/10.1016/0005-2736(90)90058-v.

    Article  CAS  PubMed  Google Scholar 

  42. Ran, S., Downes, A., and Thorpe, P. E. (2002) Increased exposure of anionic phospholipids on the surface of tumor blood vessels, Cancer Res., 62, 6132-6140.

    CAS  PubMed  Google Scholar 

  43. Zargarian, S., Shlomovitz, I., Erlich, Z., Hourizadeh, A., Ofir-Birin, Y., et al. (2017) Phosphatidylserine externalization, “necroptotic bodies” release, and phagocytosis during necroptosis, PLoS Biol., 15, e2002711, https://doi.org/10.1371/journal.pbio.2002711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Maeda, A., and Fadeel, B. (2014) Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals, Cell Death Dis., 5, e1312, https://doi.org/10.1038/cddis.2014.277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang, Q., Imamura, R., Motani, K., Kushiyama, H., Nagata, S., et al. (2013) Pyroptotic cells externalize eat-me and release find-me signals and are efficiently engulfed by macrophages, Int. Immunol., 25, 363-372, https://doi.org/10.1093/intimm/dxs161.

    Article  CAS  PubMed  Google Scholar 

  46. Klöditz, K., and Fadeel, B. (2019) Three cell deaths and a funeral: Macrophage clearance of cells undergoing distinct modes of cell death, Cell Death Discov., 5, 65, https://doi.org/10.1038/s41420-019-0146-x.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Krysko, O., De Ridder, L., and Cornelissen, M. (2004) Phosphatidylserine exposure during early primary necrosis (oncosis) in JB6 cells as evidenced by immunogold labeling technique, Apoptosis Int. J. Programm. Cell Death, 9, 495-500, https://doi.org/10.1023/B:APPT.0000031452.75162.75.

    Article  CAS  Google Scholar 

  48. Young, M. M., Bui, V., Chen, C., and Wang, H. G. (2019) FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia, Cell Death Dis., 10, 847, https://doi.org/10.1038/s41419-019-2080-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ikenouchi, J., and Aoki, K. (2017) Membrane bleb: A seesaw game of two small GTPases, Small GTPases, 8, 85-89, https://doi.org/10.1080/21541248.2016.1199266.

    Article  CAS  PubMed  Google Scholar 

  50. Khajah, M. A., and Luqmani, Y. A. (2016) Involvement of membrane blebbing in immunological disorders and cancer, Med. Princ. Pract., 25 Suppl. 2, 18-27, https://doi.org/10.1159/000441848.

    Article  PubMed  Google Scholar 

  51. Charras, G., and Paluch, E. (2008) Blebs lead the way: How to migrate without lamellipodia, Nat. Rev. Mol. Cell Biol., 9, 730-736, https://doi.org/10.1038/nrm2453.

    Article  CAS  PubMed  Google Scholar 

  52. Norman, L. L., Brugués, J., Sengupta, K., Sens, P., and Aranda-Espinoza, H. (2010) Cell blebbing and membrane area homeostasis in spreading and retracting cells, Biophys. J., 99, 1726-1733, https://doi.org/10.1016/j.bpj.2010.07.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ridley, A. J. (2011) Life at the leading edge, Cell, 145, 1012-1022, https://doi.org/10.1016/j.cell.2011.06.010.

    Article  CAS  PubMed  Google Scholar 

  54. Zatulovskiy, E., Tyson, R., Bretschneider, T., and Kay, R. R. (2014) Bleb-driven chemotaxis of Dictyostelium cells, J. Cell Biol., 204, 1027-1044, https://doi.org/10.1083/jcb.201306147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Khajah, M. A., Mathew, P. M., Alam-Eldin, N. S., and Luqmani, Y. A. (2015) Bleb formation is induced by alkaline but not acidic pH in estrogen receptor silenced breast cancer cells, Int. J. Oncol., 46, 1685-1698, https://doi.org/10.3892/ijo.2015.2884.

    Article  CAS  PubMed  Google Scholar 

  56. Karlsson, T., Bolshakova, A., Magalhães, M. A., Loitto, V. M., and Magnusson, K. E. (2013) Fluxes of water through aquaporin 9 weaken membrane-cytoskeleton anchorage and promote formation of membrane protrusions, PLoS One, 8, e59901, https://doi.org/10.1371/journal.pone.0059901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Blaser, H., Reichman-Fried, M., Castanon, I., Dumstrei, K., Marlow, F. L., et al. (2006) Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow, Dev. Cell, 11, 613-627, https://doi.org/10.1016/j.devcel.2006.09.023.

    Article  CAS  PubMed  Google Scholar 

  58. D’Andrea-Winslow, L., and Novitski, A. K. (2008) Active bleb formation is abated in Lytechinus variegatus red spherule coelomocytes after disruption of acto-myosin contractility, Integr. Zool., 3, 115-122, https://doi.org/10.1111/j.1749-4877.2008.00086.x.

    Article  PubMed  Google Scholar 

  59. Haston, W. S., and Shields, J. M. (1984) Contraction waves in lymphocyte locomotion, J. Cell Sci., 68, 227-241.

    Article  CAS  PubMed  Google Scholar 

  60. Zatulovskiy, E., and Kay, R. R. (2016) Chemotactic blebbing in dictyostelium cells, Methods Mol. Biol., 1407, 97-105, https://doi.org/10.1007/978-1-4939-3480-5_7.

    Article  CAS  PubMed  Google Scholar 

  61. Wolf, K., Mazo, I., Leung, H., Engelke, K., von Andrian, U. H., et al. (2003) Compensation mechanism in tumor cell migration: Mesenchymal-amoeboid transition after blocking of pericellular proteolysis, J. Cell Biol., 160, 267-277, https://doi.org/10.1083/jcb.200209006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bergert, M., Chandradoss, S. D., Desai, R. A., and Paluch, E. (2012) Cell mechanics control rapid transitions between blebs and lamellipodia during migration, Proc. Natl. Acad. Sci. USA, 109, 14434-14439, https://doi.org/10.1073/pnas.1207968109.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Derivery, E., Fink, J., Martin, D., Houdusse, A., Piel, M., et al. (2008) Free Brick1 is a trimeric precursor in the assembly of a functional wave complex, PLoS One, 3, e2462, https://doi.org/10.1371/journal.pone.0002462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gadea, G., de Toledo, M., Anguille, C., and Roux, P. (2007) Loss of p53 promotes RhoA-ROCK-dependent cell migration and invasion in 3D matrices, J. Cell Biol., 178, 23-30, https://doi.org/10.1083/jcb.200701120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Voura, E. B., Sandig, M., Kalnins, V. I., and Siu, C. (1998) Cell shape changes and cytoskeleton reorganization during transendothelial migration of human melanoma cells, Cell Tissue Res., 293, 375-387, https://doi.org/10.1007/s004410051129.

    Article  CAS  PubMed  Google Scholar 

  66. Maugis, B., Brugués, J., Nassoy, P., Guillen, N., Sens, P., et al. (2010) Dynamic instability of the intracellular pressure drives bleb-based motility, J. Cell Sci., 123 (Pt. 22), 3884-3892, https://doi.org/10.1242/jcs.065672.

    Article  CAS  Google Scholar 

  67. Olson, E. C. (1996) Onset of electrical excitability during a period of circus plasma membrane movements in differentiating Xenopus neurons, J. Neurosci., 16, 5117-5129, https://doi.org/10.1523/JNEUROSCI.16-16-05117.1996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kardash, E., Reichman-Fried, M., Maître, J. L., Boldajipour, B., Papusheva, E., et al. (2010) A role for Rho GTPases and cell-cell adhesion in single-cell motility in vivo, Nat. Cell Biol., 12, 47-53, https://doi.org/10.1038/ncb2003.

    Article  CAS  PubMed  Google Scholar 

  69. Charras, G. T. (2008) A short history of blebbing, J. Microsc., 231, 466-478, https://doi.org/10.1111/j.1365-2818.2008.02059.x.

    Article  CAS  PubMed  Google Scholar 

  70. Mercer, J., and Helenius, A. (2008) Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells, Science, 320, 531-535, https://doi.org/10.1126/science.1155164.

    Article  CAS  PubMed  Google Scholar 

  71. Babiychuk, E. B., Monastyrskaya, K., Potez, S., and Draeger, A. (2011) Blebbing confers resistance against cell lysis, Cell Death Differ., 18, 80-89, https://doi.org/10.1038/cdd.2010.81.

    Article  CAS  PubMed  Google Scholar 

  72. Nganga, R., Oleinik, N., Kim, J., Selvam, S. P., De Palma, R., et al. (2019) Receptor-interacting Ser/Thr kinase 1 (RIPK1) and myosin IIA-dependent ceramidosomes form membrane pores that mediate blebbing and necroptosis, J. Biol. Chem., 294, 502-519, https://doi.org/10.1074/jbc.RA118.005865.

    Article  CAS  PubMed  Google Scholar 

  73. Chen, X., He, W. T., Hu, L., Li, J., Fang, Y., et al. (2016) Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis, Cell Res., 26, 1007-1020, https://doi.org/10.1038/cr.2016.100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Sun, Y., Yu, J., Liu, X., Zhang, C., Cao, J., et al. (2018) Oncosis-like cell death is induced by berberine through ERK1/2-mediated impairment of mitochondrial aerobic respiration in gliomas, Biomed. Pharmacother., 102, 699-710, https://doi.org/10.1016/j.biopha.2018.03.132.

    Article  CAS  PubMed  Google Scholar 

  75. Ma, L. S., Jiang, C. Y., Cui, M., Lu, R., Liu, S. S., et al. (2013) Fluopsin C induces oncosis of human breast adenocarcinoma cells, Acta Pharmacol. Sin., 34, 1093-1100, https://doi.org/10.1038/aps.2013.44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sun, L., Zhao, Y., Yuan, H., Li, X., Cheng, A., et al. (2010) Solamargine, a steroidal alkaloid glycoside, induces oncosis in human K562 leukemia and squamous cell carcinoma KB cells, Cancer Chemother. Pharmacol., 67, 813-821, https://doi.org/10.1007/s00280-010-1387-9.

    Article  CAS  PubMed  Google Scholar 

  77. Simard, J. M., Woo, S. K., and Gerzanich, V. (2012) Transient receptor potential melastatin 4 and cell death, Pflüg. Arch. Eur. J. Physiol., 464, 573-582, https://doi.org/10.1007/s00424-012-1166-z.

    Article  CAS  Google Scholar 

  78. Repsold, L., and Joubert, A. M. (2018) Eryptosis: An erythrocyte’s suicidal type of cell death, BioMed Res. Int., 2018, 1-10, https://doi.org/10.1155/2018/9405617.

    Article  CAS  Google Scholar 

  79. Naveed, A., Jilani, K., Siddique, A. B., Akbar, M., Riaz, M., et al. (2020) Induction of erythrocyte shrinkage by omeprazole, Dose Response, 18, https://doi.org/10.1177/1559325820946941.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Shalini, S., Dorstyn, L., Dawar, S., and Kumar, S. (2015) Old, new and emerging functions of caspases, Cell Death Differ., 22, 526-539, https://doi.org/10.1038/cdd.2014.216.

    Article  CAS  PubMed  Google Scholar 

  81. Julien, O., and Wells, J. A. (2017) Caspases and their substrates, Cell Death Differ., 24, 1380-1389, https://doi.org/10.1038/cdd.2017.44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Lamkanfi, M., Festjens, N., Declercq, W., Vanden Berghe, T., and Vandenabeele, P. (2007) Caspases in cell survival, proliferation and differentiation, Cell Death Differ., 14, 44-55, https://doi.org/10.1038/sj.cdd.4402047.

    Article  CAS  PubMed  Google Scholar 

  83. Fan, W., Dai, Y., Xu, H., Zhu, X., Cai, P., et al. (2014) Caspase-3 modulates regenerative response after stroke, Stem Cells, 32, 473-486, https://doi.org/10.1002/stem.1503.

    Article  CAS  PubMed  Google Scholar 

  84. Baena-Lopez, L. A., Arthurton, L., Xu, D. C., and Galasso, A. (2018) Non-apoptotic Caspase regulation of stem cell properties, Semin. Cell Dev. Biol., 82, 118-126, https://doi.org/10.1016/j.semcdb.2017.10.034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Fujita, J., Crane, A. M., Souza, M. K., Dejosez, M., Kyba, M., et al. (2008) Caspase activity mediates the differentiation of embryonic stem cells, Cell Stem Cell, 2, 595-601, https://doi.org/10.1016/j.stem.2008.04.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Fernando, P., Kelly, J. F., Balazsi, K., Slack, R. S., and Megeney, L. A. (2002) Caspase 3 activity is required for skeletal muscle differentiation, Proc. Natl. Acad. Sci. USA, 99, 11025-11030, https://doi.org/10.1073/pnas.162172899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kim, J.-S., Ha, J.-Y., Yang, S., and Son, J. H. (2017) A novel non-apoptotic role of procaspase-3 in the regulation of mitochondrial biogenesis activators, J. Cell. Biochem., 119, 347-357, https://doi.org/10.1002/jcb.26186.

    Article  CAS  PubMed  Google Scholar 

  88. Huang, Q., Li, F., Liu, X., Li, W., Shi, W., et al. (2011) Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy, Nat. Med., 17, 860-866, https://doi.org/10.1038/nm.2385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Shen, X., Venero, J. L., Joseph, B., and Burguillos, M. A. (2018) Caspases orchestrate microglia instrumental functions, Progr. Neurobiol., 171, 50-71, https://doi.org/10.1016/j.pneurobio.2018.09.007.

    Article  CAS  Google Scholar 

  90. Maelfait, J., Vercammen, E., Janssens, S., Schotte, P., Haegman, M., et al. (2008) Stimulation of Toll-like receptor 3 and 4 induces interleukin-1beta maturation by caspase-8, J. Exp. Med., 205, 1967-1973, https://doi.org/10.1084/jem.20071632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gurung, P., and Kanneganti, T. D. (2015) Novel roles for caspase-8 in IL-1β and inflammasome regulation, Am. J. Pathol., 185, 17-25, https://doi.org/10.1016/j.ajpath.2014.08.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Schwarzer, R., Laurien, L., and Pasparakis, M. (2020) New insights into the regulation of apoptosis, necroptosis, and pyroptosis by receptor interacting protein kinase 1 and caspase-8, Curr. Opin. Cell Biol., 63, 186-193, https://doi.org/10.1016/j.ceb.2020.02.004.

    Article  CAS  PubMed  Google Scholar 

  93. Xia, S., Hollingsworth, L. R., 4th, and Wu, H. (2020) Mechanism and regulation of gasdermin-mediated cell death, Cold Spring Harb Perspect Biol., 12, a036400, https://doi.org/10.1101/cshperspect.a036400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Geisbrecht, E. R., and Montell, D. J. (2004) A role for Drosophila IAP1-mediated caspase in-hibition in Rac-dependent cell migration, Cell, 118, 111-125, https://doi.org/10.1016/j.cell.2004.06.020.

    Article  CAS  PubMed  Google Scholar 

  95. Graf, R. P., Keller, N., Barbero, S., and Stupack, D. (2014) Caspase-8 as a regulator of tumor cell motility, Curr. Mol. Med., 14, 246-254, https://doi.org/10.2174/1566524014666140128111951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Torres, V. A., Mielgo, A., Barbero, S., Hsiao, R., Wilkins, J. A., et al. (2010) Rab5 mediates caspase-8-promoted cell motility and metastasis, Mol. Biol. Cell, 21, 369-376, https://doi.org/10.1091/mbc.e09-09-0769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Aram, L., Yakobi-Sharon, K., and Arama, E. (2017) CDPs: Caspase-dependent non-lethal cellular processes, Cell Death Differ., 24, 1307-1310, https://doi.org/10.1038/cdd.2017.111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Espinosa-Oliva, A.M., García-Revilla, J., Alonso-Bellido, I. M., and Burguillos, M. A. (2019) Brainiac caspases: Beyond the wall of apoptosis, Front. Cell Neurosci., 13, 500, https://doi.org/10.3389/fncel.2019.00500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was financially supported by the Russian Foundation for Basic Research (grant no. 19-015-00233a).

Author information

Authors and Affiliations

  1. Faculty of Biology, Lomonosov Moscow State University, 119234, Moscow, Russia

    Margarita A. Savitskaya, Ilya I. Zakharov & Galina E. Onishchenko

Authors
  1. Margarita A. Savitskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilya I. Zakharov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Galina E. Onishchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Galina E. Onishchenko.

Ethics declarations

The authors declare no conflicts of interest. This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Savitskaya, M.A., Zakharov, I.I. & Onishchenko, G.E. Apoptotic Features in Non-Apoptotic Processes. Biochemistry Moscow 87, 191–206 (2022). https://doi.org/10.1134/S0006297922030014

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297922030014

Keywords

Search

Navigation