The potential role of acrolein in plant ferroptosis-like cell death

Autoři: Péter Hajdinák aff001;  Ádám Czobor aff001;  András Szarka aff001
Působiště autorů: Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Budapest University of Technology and Economics, Budapest, Hungary aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227278


The iron dependent, programmed cell death, ferroptosis was described first in tumour cells. It showed distinct features from the already known cell death forms such as apoptosis, necrosis and autophagy. The caspase independent cell death could be induced by the depletion of glutathione by erastin or by the inhibition of the lipid peroxide scavenger enzyme GPX4 by RSL3 and it was accompanied by the generation of lipid reactive oxygen species. Recently, ferroptosis-like cell death associated to glutathione depletion, lipid peroxidation and iron dependency could also be induced in plant cells by heat treatment. Unfortunately, the mediators and elements of the ferroptotic pathway have not been described yet. Our present results on Arabidopsis thaliana cell cultures suggest that acrolein, a lipid peroxide-derived reactive carbonyl species, is involved in plant ferroptosis-like cell death. The acrolein induced cell death could be mitigated by the known ferroptosis inhibitors such as Ferrostatin-1, Deferoxamine, α-Tocopherol, and glutathione. At the same time acrolein can be a mediator of ferroptosis-like cell death in plant cells since the known ferroptosis inducer RSL3 induced cell death could be mitigated by the acrolein scavenger carnosine. Finally, on the contrary to the caspase independent ferroptosis in human cells, we found that caspase-like activity can be involved in plant ferroptosis-like cell death.

Klíčová slova:

Arabidopsis thaliana – Cell death – Glutathione – Lipid peroxidation – Plant cells – Proteases – Thermal stresses – Peroxides


1. Szarka A, Tomasskovics B, Bánhegyi G. The ascorbate-glutathione-α-tocopherol triad in abiotic stress response. Int J Mol Sci. 2012;13: 4458–83. doi: 10.3390/ijms13044458 22605990

2. Czobor Á, Hajdinák P, Szarka A. Rapid ascorbate response to bacterial elicitor treatment in Arabidopsis thaliana cells. Acta Physiol Plant. 2017;39: 62. doi: 10.1007/s11738-017-2365-1

3. Czobor Á, Hajdinák P, Németh B, Piros B, Németh Á, Szarka A. Comparison of the response of alternative oxidase and uncoupling proteins to bacterial elicitor induced oxidative burst. Balestrini R, editor. PLoS One. 2019;14: e0210592. doi: 10.1371/journal.pone.0210592 30629714

4. Van Aken O, Van Breusegem F. Licensed to Kill: Mitochondria, Chloroplasts, and Cell Death. Trends Plant Sci. 2015;20: 754–766. doi: 10.1016/j.tplants.2015.08.002 26442680

5. Zhou DR, Eid R, Boucher E, Miller KA, Mandato CA, Greenwood MT. Stress is an agonist for the induction of programmed cell death: A review. Biochim Biophys Acta—Mol Cell Res. 2019;1866: 699–712. doi: 10.1016/j.bbamcr.2018.12.001 30529230

6. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149: 1060–72. doi: 10.1016/j.cell.2012.03.042 22632970

7. Fearnhead HO, Vandenabeele P, Berghe T Vanden. How do we fit ferroptosis in the family of regulated cell death? Cell Death and Differentiation. Nature Publishing Group; 2017. pp. 1991–1998. doi: 10.1038/cdd.2017.149 28984871

8. Yin H, Xu L, Porter NA. Free Radical Lipid Peroxidation: Mechanisms and Analysis. Chem Rev. 2011;111: 5944–5972. doi: 10.1021/cr200084z 21861450

9. Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, et al. Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 2014;3: 1–25. doi: 10.7554/eLife.02523 24844246

10. Distéfano AM, Martin MV, Córdoba JP, Bellido AM, D’Ippólito S, Colman SL, et al. Heat stress induces ferroptosis-like cell death in plants. J Cell Biol. 2017;216: 463–476. doi: 10.1083/jcb.201605110 28100685

11. Dangol S, Chen Y, Hwang BK, Jwa N. Iron- and Reactive Oxygen Species-Dependent Ferroptotic Cell Death in Rice- Magnaporthe oryzae Interactions. Plant Cell. 2019;31: 189–209. doi: 10.1105/tpc.18.00535 30563847

12. Conrad M, Kagan VE, Bayir H, Pagnussat GC, Head B, Traber MG, et al. Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev. 2018;32: 602–619. doi: 10.1101/gad.314674.118 29802123

13. Mano J. Reactive carbonyl species: Their production from lipid peroxides, action in environmental stress, and the detoxification mechanism. Plant Physiol Biochem. 2012;59: 90–97. doi: 10.1016/j.plaphy.2012.03.010 22578669

14. Grosch W. Reactions of hydroperoxidesdproducts of low molecular weight. Autoxidation of Unsaturated Lipids. Academic Press; 1987. pp. 95–139. Available:

15. Biswas MS, Mano J. Reactive carbonyl species activate caspase-3-like protease to initiate programmed cell death in plants. Plant Cell Physiol. 2016;57: 1432–1442. doi: 10.1093/pcp/pcw053 27106783

16. Hajdinák P, Czobor Á, Lőrincz T, Szarka A. The Problem of Glutathione Determination: a Comparative Study on the Measurement of Glutathione from Plant Cells. Period Polytech Chem Eng. 2018;63: 1–10. doi: 10.3311/PPch.11785

17. Castro-concha LA, Escobedo RM, Miranda-ham MDL. Measurement of Cell Viability in In Vitro Cultures. Methods Mol Biol. 2006;318: 71–76. doi: 10.1385/1-59259-959-1:071 16673906

18. Hodges DM, DeLong JM, Forney CF, Prange RK. Improving the thiobarbituric acid-reactive-substances assay for estimating lipid peroxidation in plant tissues containing anthocyanin and other interfering compounds. Planta. 1999;207: 604–611. doi: 10.1007/s004250050524

19. Poborilova Z, Opatrilova R, Babula P. Toxicity of aluminium oxide nanoparticles demonstrated using a BY-2 plant cell suspension culture model. Environ Exp Bot. 2013;91: 1–11. doi: 10.1016/j.envexpbot.2013.03.002

20. García-Heredia JM, Hervás M, De La Rosa MA, Navarro JA. Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures. Planta. 2008;228: 89–97. doi: 10.1007/s00425-008-0721-5 18335236

21. Biswas MS, Mano J. Lipid Peroxide-Derived Short-Chain Carbonyls Mediate Hydrogen Peroxide-Induced and Salt-Induced Programmed Cell Death in Plants. Plant Physiol. 2015;168: 885–898. doi: 10.1104/pp.115.256834 26025050

22. Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol. 2008;15: 234–45. doi: 10.1016/j.chembiol.2008.02.010 18355723

23. Stockwell BR, Dolma S, Lessnick SL, Hahn WC. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell. 2003;3: 285–96. Available: doi: 10.1016/s1535-6108(03)00050-3 12676586

24. Dächert J, Schoeneberger H, Rohde K, Fulda S. RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death. Oncotarget. 2016;7: 63779–63792. doi: 10.18632/oncotarget.11687 27588473

25. Pan X, Lin Z, Jiang D, Yu Y, Yang D, Zhou H, et al. Erastin decreases radioresistance of NSCLC cells partially by inducing GPX4‑mediated ferroptosis. Oncol Lett. 2019;17: 3001–3008. doi: 10.3892/ol.2019.9888 30854078

26. Qu G-Q, Liu X, Zhang Y-L, Yao D, Ma Q-M, Yang M-Y, et al. Evidence for programmed cell death and activation of specific caspase-like enzymes in the tomato fruit heat stress response. Planta. 2009;229: 1269–1279. doi: 10.1007/s00425-009-0908-4 19296126

27. Zsigmond L, Tomasskovics B, Deák V, Rigó G, Szabados L, Bánhegyi G, et al. Enhanced activity of galactono-1,4-lactone dehydrogenase and ascorbate-glutathione cycle in mitochondria from complex III deficient Arabidopsis. Plant Physiol Biochem. 2011;49: 809–15. doi: 10.1016/j.plaphy.2011.04.013 21601466

28. Lőrincz T, Jemnitz K, Kardon T, Mandl J, Szarka A. Ferroptosis is Involved in Acetaminophen Induced Cell Death. Pathol Oncol Res. 2015;21: 1115–1121. doi: 10.1007/s12253-015-9946-3 25962350

29. Hao S, Liang B, Huang Q, Dong S, Wu Z, He W, et al. Metabolic networks in ferroptosis (Review). Oncol Lett. 2018;15: 5405–5411. doi: 10.3892/ol.2018.8066 29556292

30. Yang WS, Sriramaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156: 317–331. doi: 10.1016/j.cell.2013.12.010 24439385

Článek vyšel v časopise


2019 Číslo 12