Abstract
Reactive oxygen species (ROS) mediate lipid peroxidation and produce 4-hydroxynonenal and other related products, which play an important role in the process of cell death, including apoptosis, autophagy, and ferroptosis. Lipid peroxidation of phospholipid bilayers can promote mitochondrial apoptosis, endoplasmic reticulum stress, and other complex molecular signaling pathways to regulate apoptosis. Lipid peroxidation and its products also act at different stages of autophagy, affecting the formation of autophagosomes and the recruitment of downstream proteins. In addition, we discuss the important role of ROS and lipid peroxides in ferroptosis and the regulatory role of nuclear factor erythroid 2-related factor 2 in ferroptosis under a background of oxidation. Finally, from the perspectives of promotion, inhibition, transformation, and common upstream molecules, we summarized the crosstalk among apoptosis, autophagy, and ferroptosis in the context of ROS. Our review discusses the role of ROS and lipid peroxidation in apoptosis, autophagy, and ferroptosis and their possible crosstalk mechanisms, so as to provide new insights and directions for the study of diseases related to pathological cell death. This review also has referential significance for studying the exact mechanism of ferroptosis mediated by lipid peroxidation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Data sharing is not applicable to this article as no new data were created or analyzed in this review.
References
Agrawal S, Fox J, Thyagarajan B, Fox JH (2018) Brain mitochondrial iron accumulates in Huntington’s disease, mediates mitochondrial dysfunction, and can be removed pharmacologically. Free Radical Biol Med 120:317–329. https://doi.org/10.1016/j.freeradbiomed.2018.04.002
Ahmad S, Khan H, Shahab U et al (2017) Protein oxidation: an overview of metabolism of sulphur containing amino acid, cysteine. Front Biosci (schol Ed) 9:71–87
Awasthi YC, Sharma R, Cheng JZ et al (2003) Role of 4-hydroxynonenal in stress-mediated apoptosis signaling. Mol Aspects Med 24:219–230
Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Med Cellular Longev 2014:360438. https://doi.org/10.1155/2014/360438
Bai Y, Meng L, Han L et al (2019) Lipid storage and lipophagy regulates ferroptosis. Biochem Biophys Res Commun 508:997–1003. https://doi.org/10.1016/j.bbrc.2018.12.039
Barbour V (2002) Celebrating death–the 2002 Nobel prize in physiology or medicine. Lancet (London, England) 360(9340):1117
Basit F, van Oppen LM, Schöckel L et al (2017) Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell Death Dis 8:e2716. https://doi.org/10.1038/cddis.2017.133
Bayir H (2005) Reactive oxygen species. Crit Care Med 33:S498-501
Bernardi P, Di Lisa F (2015) The mitochondrial permeability transition pore: molecular nature and role as a target in cardioprotection. J Mol Cell Cardiol 78:100–106. https://doi.org/10.1016/j.yjmcc.2014.09.023
Bock FJ, Tait SWG (2020) Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. https://doi.org/10.1038/s41580-019-0173-8
Bou-Teen D, Kaludercic N, Weissman D et al (2021) Mitochondrial ROS and mitochondria-targeted antioxidants in the aged heart. Free Radical Biol Med 167:109–124. https://doi.org/10.1016/j.freeradbiomed.2021.02.043
Brynildsen MP, Winkler JA, Spina CS, MacDonald IC, Collins JJ (2013) Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production. Nat Biotechnol 31(2):160–165. https://doi.org/10.1038/nbt.2458
Chang L-C, Chiang S-K, Chen S-E, Yu Y-L, Chou R-H, Chang W-C (2018) Heme oxygenase-1 mediates BAY 11–7085 induced ferroptosis. Cancer Lett 416:124–137. https://doi.org/10.1016/j.canlet.2017.12.025
Chen X, Xu S, Zhao C, Liu B (2019) Role of TLR4/NADPH oxidase 4 pathway in promoting cell death through autophagy and ferroptosis during heart failure. Biochem Biophys Res Commun 516:37–43. https://doi.org/10.1016/j.bbrc.2019.06.015
Chen X, Kang R, Kroemer G, Tang D (2021) Organelle-specific regulation of ferroptosis. Cell Death Differ 28(10):2843–2856. https://doi.org/10.1038/s41418-021-00859-z
Chiarpotto E, Domenicotti C, Paola D et al (1999) Regulation of rat hepatocyte protein kinase C beta isoenzymes by the lipid peroxidation product 4-hydroxy-2,3-nonenal: a signaling pathway to modulate vesicular transport of glycoproteins. Hepatology (Baltimore, MD) 29:1565–1572
Crawford ED, Seaman JE, Agard N et al (2013) The DegraBase: a database of proteolysis in healthy and apoptotic human cells. Mol Cell Proteom 12:813–824. https://doi.org/10.1074/mcp.O112.024372
Csala M, Kardon T, Legeza B et al (2015) On the role of 4-hydroxynonenal in health and disease. Biochem Biophys Acta 1852:826–838. https://doi.org/10.1016/j.bbadis.2015.01.015
Das UN (1999) Essential fatty acids, lipid peroxidation and apoptosis. Prostaglandins Leukot Essent Fatty Acids 61:157–163
Davies KJA (2016) Adaptive homeostasis. Mol Aspects Med 49:1–7. https://doi.org/10.1016/j.mam.2016.04.007
DeHart DN, Fang D, Heslop K, Li L, Lemasters JJ, Maldonado EN (2018) Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells. Biochem Pharmacol 148:155–162. https://doi.org/10.1016/j.bcp.2017.12.022
Dixon SJ, Lemberg KM, Lamprecht MR et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072. https://doi.org/10.1016/j.cell.2012.03.042
Dodson M, Castro-Portuguez R, Zhang DD (2019) NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 23:101107. https://doi.org/10.1016/j.redox.2019.101107
Dolinsky VW, Chan AYM, Robillard Frayne I, Light PE, Des Rosiers C, Dyck JRB (2009) Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Circulation 119:1643–1652. https://doi.org/10.1161/CIRCULATIONAHA.108.787440
Doll S, Conrad M (2017) Iron and ferroptosis: a still ill-defined liaison. IUBMB Life 69:423–434. https://doi.org/10.1002/iub.1616
Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1):47–95
Edenharter O, Schneuwly S, Navarro JA (2018) Mitofusin-dependent ER stress triggers glial dysfunction and nervous system degeneration in a drosophila model of Friedreich’s ataxia. Front Mol Neurosci 11:38. https://doi.org/10.3389/fnmol.2018.00038
Elkin ER, Harris SM, Loch-Caruso R (2018) Trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line. Toxicol Appl Pharmacol 338:30–42. https://doi.org/10.1016/j.taap.2017.11.006
Esterbauer H, Cheeseman KH, Dianzani MU, Poli G, Slater TF (1982) Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes. Biochem J 208:129–140
Forman HJ, Dickinson DA, Iles KE (2003) HNE–signaling pathways leading to its elimination. Mol Aspects Med 24:189–194
Fruhwirth GO, Loidl A, Hermetter A (2007) Oxidized phospholipids: from molecular properties to disease. Biochem Biophys Acta 1772:718–736
Fukui M, Kang KS, Okada K, Zhu BT (2013) EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. J Cell Biochem 114:192–203. https://doi.org/10.1002/jcb.24354
Gao M, Jiang X (2018) To eat or not to eat-the metabolic flavor of ferroptosis. Curr Opin Cell Biol 51:58–64. https://doi.org/10.1016/j.ceb.2017.11.001
Gao M, Yi J, Zhu J et al (2019) Role of mitochondria in ferroptosis. Mol Cell 73:354-363.e3. https://doi.org/10.1016/j.molcel.2018.10.042
Gao L, Loveless J, Shay C, Teng Y (2020) Targeting ROS-mediated crosstalk between autophagy and apoptosis in cancer. Adv Exp Med Biol 1260:1–12. https://doi.org/10.1007/978-3-030-42667-5_1
Gaschler MM, Andia AA, Liu H et al (2018) FINO(2) initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat Chem Biol 14:507–515. https://doi.org/10.1038/s41589-018-0031-6
Guo X-L, Li D, Hu F et al (2012) Targeting autophagy potentiates chemotherapy-induced apoptosis and proliferation inhibition in hepatocarcinoma cells. Cancer Lett 320:171–179. https://doi.org/10.1016/j.canlet.2012.03.002
Haberzettl P, Hill BG (2013) Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response. Redox Biol 1:56–64. https://doi.org/10.1016/j.redox.2012.10.003
Harada N, Kanayama M, Maruyama A et al (2011) Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages. Arch Biochem Biophys 508:101–109. https://doi.org/10.1016/j.abb.2011.02.001
Hill BG, Haberzettl P, Ahmed Y, Srivastava S, Bhatnagar A (2008) Unsaturated lipid peroxidation-derived aldehydes activate autophagy in vascular smooth-muscle cells. Biochem J 410:525–534
Hong SH, Lee D-H, Lee Y-S et al (2017) Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression. Oncotarget 8:115164–115178. https://doi.org/10.18632/oncotarget.23046
Hou W, Xie Y, Song X et al (2016) Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12:1425–1428. https://doi.org/10.1080/15548627.2016.1187366
Huang J, Chen S, Hu L et al (2018) Mitoferrin-1 is Involved in the Progression of Alzheimer’s Disease Through Targeting Mitochondrial Iron Metabolism in a Caenorhabditis elegans Model of Alzheimer’s disease. Neuroscience 385:90–101. https://doi.org/10.1016/j.neuroscience.2018.06.011
Huo H, Zhou Z, Qin J, Liu W, Wang B, Gu Y (2016) Erastin disrupts mitochondrial permeability transition pore (mPTP) and induces apoptotic death of colorectal cancer cells. PloS one 11:e0154605. https://doi.org/10.1371/journal.pone.0154605
Jelinek A, Heyder L, Daude M et al (2018) Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radical Biol Med 117:45–57. https://doi.org/10.1016/j.freeradbiomed.2018.01.019
Jiang X, Stockwell BR, Conrad M (2021) Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 22:266–282. https://doi.org/10.1038/s41580-020-00324-8
Jiang N, Huang R, Zhang J et al (2022) TIMP2 mediates endoplasmic reticulum stress contributing to sepsis-induced acute kidney injury. Faseb j 36(4):e22228. https://doi.org/10.1096/fj.202101555RR
Jin S, Zhou F, Katirai F, Li P-L (2011) Lipid raft redox signaling: molecular mechanisms in health and disease. Antioxid Redox Signal 15:1043–1083. https://doi.org/10.1089/ars.2010.3619
Kajarabille N, Latunde-Dada GO (2019) Programmed cell-death by ferroptosis: antioxidants as mitigators. Int J Mol Sci. https://doi.org/10.3390/ijms20194968
Kaminskyy VO, Zhivotovsky B (2014) Free radicals in cross talk between autophagy and apoptosis. Antioxid Redox Signal 21:86–102. https://doi.org/10.1089/ars.2013.5746
Kang R, Kroemer G, Tang D (2019) The tumor suppressor protein p53 and the ferroptosis network. Free Radical Biol Med 133:162–168. https://doi.org/10.1016/j.freeradbiomed.2018.05.074
Kapralov AA, Yang Q, Dar HH et al (2020) Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death. Nat Chem Biol 16:278–290. https://doi.org/10.1038/s41589-019-0462-8
Kerins MJ, Ooi A (2018) The roles of NRF2 in modulating cellular iron homeostasis. Antioxid Redox Signal 29:1756–1773. https://doi.org/10.1089/ars.2017.7176
Kinnunen PKJ, Kaarniranta K, Mahalka AK (2012) Protein-oxidized phospholipid interactions in cellular signaling for cell death: from biophysics to clinical correlations. Biochem Biophys Acta 1818:2446–2455. https://doi.org/10.1016/j.bbamem.2012.04.008
Kinowaki Y, Kurata M, Ishibashi S et al (2018) Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma. Lab Investig 98:609–619. https://doi.org/10.1038/s41374-017-0008-1
Krijt M, Jirkovska A, Kabickova T, Melenovsky V, Petrak J, Vyoral D (2018) Detection and quantitation of iron in ferritin, transferrin and labile iron pool (LIP) in cardiomyocytes using (55)Fe and storage phosphorimaging. Biochim Biophys Acta 1862:2895–2901. https://doi.org/10.1016/j.bbagen.2018.09.005
Kruiswijk F, Labuschagne CF, Vousden KH (2015) p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol 16:393–405. https://doi.org/10.1038/nrm4007
Kuang F, Liu J, Tang D, Kang R (2020) Oxidative damage and antioxidant defense in ferroptosis. Front Cell Develop Biol 8:586578. https://doi.org/10.3389/fcell.2020.586578
Kwon M-Y, Park E, Lee S-J, Chung SW (2015) Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. Oncotarget 6:24393–24403
Lee Y-S, Lee D-H, Jeong SY et al (2019) Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5. J Cell Biochem 120:928–939. https://doi.org/10.1002/jcb.27456
Lee H, Zandkarimi F, Zhang Y et al (2020a) Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol 22:225–234. https://doi.org/10.1038/s41556-020-0461-8
Lee Y-S, Kalimuthu K, Park YS et al (2020b) BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis. Apoptosis 25:625–631. https://doi.org/10.1007/s10495-020-01627-z
Li J, Sharma R, Patrick B et al (2006) Regulation of CD95 (Fas) expression and Fas-mediated apoptotic signaling in HLE B-3 cells by 4-hydroxynonenal. Biochemistry 45:12253–12264
Li C, Zhang Y, Liu J, Kang R, Klionsky DJ, Tang D (2021) Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. Autophagy 17:948–960. https://doi.org/10.1080/15548627.2020.1739447
Lin M-H, Yen J-H, Weng C-Y, Wang L, Ha C-L, Wu M-J (2014) Lipid peroxidation end product 4-hydroxy-trans-2-nonenal triggers unfolded protein response and heme oxygenase-1 expression in PC12 cells: Roles of ROS and MAPK pathways. Toxicology 315:24–37. https://doi.org/10.1016/j.tox.2013.11.007
Liu J, Kuang F, Kroemer G, Klionsky DJ, Kang R, Tang D (2020) Autophagy-dependent ferroptosis: machinery and regulation. Cell Chem Biol 27:420–435. https://doi.org/10.1016/j.chembiol.2020.02.005
Liu Y, Wang Y, Liu J, Kang R, Tang D (2021) Interplay between MTOR and GPX4 signaling modulates autophagy-dependent ferroptotic cancer cell death. Cancer Gene Ther 28:55–63. https://doi.org/10.1038/s41417-020-0182-y
Lv H, Zhen C, Liu J, Yang P, Hu L, Shang P (2019) Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxid Med Cell Longev 2019:3150145. https://doi.org/10.1155/2019/3150145
Martinez-Useros J, Garcia-Foncillas J (2016) Obesity and colorectal cancer: molecular features of adipose tissue. J Transl Med 14:21. https://doi.org/10.1186/s12967-016-0772-5
Mikami K, Murata N (2003) Membrane fluidity and the perception of environmental signals in cyanobacteria and plants. Prog Lipid Res 42(6):527–543
Moloney JN, Cotter TG (2018) ROS signalling in the biology of cancer. Semin Cell Dev Biol 80:50–64. https://doi.org/10.1016/j.semcdb.2017.05.023
Neitemeier S, Jelinek A, Laino V et al (2017) BID links ferroptosis to mitochondrial cell death pathways. Redox Biol 12:558–570. https://doi.org/10.1016/j.redox.2017.03.007
Ogata M, Hino S-i, Saito A et al (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26:9220–9231
Page S, Fischer C, Baumgartner B et al (1999) 4-Hydroxynonenal prevents NF-kappaB activation and tumor necrosis factor expression by inhibiting IkappaB phosphorylation and subsequent proteolysis. J Biol Chem 274:11611–11618
Park E, Chung SW (2019) ROS-mediated autophagy increases intracellular iron levels and ferroptosis by. Cell Death Dis 10:822. https://doi.org/10.1038/s41419-019-2064-5
Paul BT, Manz DH, Torti FM, Torti SV (2017) Mitochondria and iron: current questions. Expert Rev Hematol 10:65–79. https://doi.org/10.1080/17474086.2016.1268047
Pizzimenti S, Ciamporcero E, Daga M et al (2013) Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Front Physiol 4:242. https://doi.org/10.3389/fphys.2013.00242
Poli G, Dianzani MU, Cheeseman KH, Slater TF, Lang J, Esterbauer H (1985) Separation and characterization of the aldehydic products of lipid peroxidation stimulated by carbon tetrachloride or ADP-iron in isolated rat hepatocytes and rat liver microsomal suspensions. Biochem J 227:629–638
Preston GA, Zarella CS, Pendergraft WFr, et al. (2002) Novel effects of neutrophil-derived proteinase 3 and elastase on the vascular endothelium involve in vivo cleavage of NF-kappaB and proapoptotic changes in JNK, ERK, and p38 MAPK signaling pathways. J Am Soc Nephrol 13:2840-2849
Sasaki H, Sato H, Kuriyama-Matsumura K et al (2002) Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression. J Biol Chem 277:44765–44771
Sharma R, Sharma A, Dwivedi S, Zimniak P, Awasthi S, Awasthi YC (2008) 4-Hydroxynonenal self-limits fas-mediated DISC-independent apoptosis by promoting export of Daxx from the nucleus to the cytosol and its binding to Fas. Biochemistry 47:143–156
Shin D, Kim EH, Lee J, Roh J-L (2018) Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radical Biol Med 129:454–462. https://doi.org/10.1016/j.freeradbiomed.2018.10.426
Sies H (2015) Oxidative stress: a concept in redox biology and medicine. Redox Biol 4:180–183. https://doi.org/10.1016/j.redox.2015.01.002
Sies H, Belousov VV, Chandel NS et al (2022) Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat Rev Mol Cell Biol 23(7):499–515. https://doi.org/10.1038/s41580-022-00456-z
Silva I, Rausch V, Peccerella T, Millonig G, Seitz H-K, Mueller S (2018) Hypoxia enhances H(2)O(2)-mediated upregulation of hepcidin: Evidence for NOX4-mediated iron regulation. Redox Biol 16:1–10. https://doi.org/10.1016/j.redox.2018.02.005
Song X, Zhu S, Chen P et al (2018) AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system X(c)(-) activity. Curr Biol 28:2388-2399.e5. https://doi.org/10.1016/j.cub.2018.05.094
Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD (2019) ROS and the DNA damage response in cancer. Redox Biol 25:101084. https://doi.org/10.1016/j.redox.2018.101084
Stockwell BR, Friedmann Angeli JP, Bayir H et al (2017) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171:273–285. https://doi.org/10.1016/j.cell.2017.09.021
Strzyz P (2020) Iron expulsion by exosomes drives ferroptosis resistance. Nat Rev Mol Cell Biol 21:4–5
Sun X, Ou Z, Chen R et al (2016) Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology (Baltimore, MD) 63:173–184. https://doi.org/10.1002/hep.28251
Suttner DM, Dennery PA (1999) Reversal of HO-1 related cytoprotection with increased expression is due to reactive iron. FASEB J 13:1800–1809
Tang Q, Chen H, Mai Z et al (2022) Bim- and Bax-mediated mitochondrial pathway dominates abivertinib-induced apoptosis and ferroptosis. Free Radical Biol Med 180:198–209. https://doi.org/10.1016/j.freeradbiomed.2022.01.013
Tower J (2015) Programmed cell death in aging. Ageing Res Rev. https://doi.org/10.1016/j.arr.2015.04.002
Tsuzuki T, Kambe T, Shibata A, Kawakami Y, Nakagawa K, Miyazawa T (2007) Conjugated EPA activates mutant p53 via lipid peroxidation and induces p53-dependent apoptosis in DLD-1 colorectal adenocarcinoma human cells. Biochem Biophys Acta 1771:20–30
Turell L, Zeida A, Trujillo M (2020) Mechanisms and consequences of protein cysteine oxidation: the role of the initial short-lived intermediates. Essays Biochem 64:55–66. https://doi.org/10.1042/EBC20190053
Ursini F, Maiorino M, Forman HJ (2016) Redox homeostasis: the Golden Mean of healthy living. Redox Biol 8:205–215. https://doi.org/10.1016/j.redox.2016.01.010
Velez JM, Miriyala S, Nithipongvanitch R et al (2011) p53 regulates oxidative stress-mediated retrograde signaling: a novel mechanism for chemotherapy-induced cardiac injury. PloS one 6:e18005. https://doi.org/10.1371/journal.pone.0018005
Volinsky R, Kinnunen PKJ (2013) Oxidized phosphatidylcholines in membrane-level cellular signaling: from biophysics to physiology and molecular pathology. FEBS J 280:2806–2816. https://doi.org/10.1111/febs.12247
Wang Y-Q, Chang S-Y, Wu Q et al (2016) The protective role of mitochondrial ferritin on erastin-induced ferroptosis. Front Aging Neurosci 8:308. https://doi.org/10.3389/fnagi.2016.00308
Wang T-T, Yang Y, Wang F, Yang W-G, Zhang J-J, Zou Z-Q (2021) Docosahexaenoic acid monoglyceride induces apoptosis and autophagy in breast cancer cells via lipid peroxidation-mediated endoplasmic reticulum stress. J Food Sci 86:4704–4716. https://doi.org/10.1111/1750-3841.15900
Wilde L, Roche M, Domingo-Vidal M et al (2017) Metabolic coupling and the reverse Warburg effect in cancer: implications for novel biomarker and anticancer agent development. Semin Oncol 44(3):198–203. https://doi.org/10.1053/j.seminoncol.2017.10.004
Wu Z, Geng Y, Lu X et al (2019) Chaperone-mediated autophagy is involved in the execution of ferroptosis. Proc Natl Acad Sci USA 116:2996–3005. https://doi.org/10.1073/pnas.1819728116
Xie Y, Zhu S, Song X et al (2017) The tumor suppressor p53 limits Ferroptosis by blocking DPP4 activity. Cell Rep 20:1692–1704. https://doi.org/10.1016/j.celrep.2017.07.055
Yang H, Magilnick N, Lee C et al (2005) Nrf1 and Nrf2 regulate rat glutamate-cysteine ligase catalytic subunit transcription indirectly via NF-kappaB and AP-1. Mol Cell Biol 25:5933–5946
Yang WS, SriRamaratnam R, Welsch ME et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–331. https://doi.org/10.1016/j.cell.2013.12.010
Yang M, Chen P, Liu J et al (2019) Clockophagy is a novel selective autophagy process favoring ferroptosis. Sci Adv 5:eaaw2238. https://doi.org/10.1126/sciadv.aaw2238
Yang W-H, Huang Z, Wu J, Ding C-KC, Murphy SK, Chi J-T (2020) A TAZ-ANGPTL4-NOX2 axis regulates ferroptotic cell death and chemoresistance in epithelial ovarian cancer. Mol Cancer Res 18:79–90. https://doi.org/10.1158/1541-7786.MCR-19-0691
Yousefi S, Perozzo R, Schmid I et al (2006) Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 8:1124–1132
Yu X, Long YC (2016) Crosstalk between cystine and glutathione is critical for the regulation of amino acid signaling pathways and ferroptosis. Sci Rep 6:30033. https://doi.org/10.1038/srep30033
Zhang J, Burrington CM, Davenport SK et al (2014) PKCδ regulates hepatic triglyceride accumulation and insulin signaling in Lepr(db/db) mice. Biochem Biophys Res Commun 450:1619–1625. https://doi.org/10.1016/j.bbrc.2014.07.048
Zhang Z, Yao Z, Wang L et al (2018) Activation of ferritinophagy is required for the RNA-binding protein ELAVL1/HuR to regulate ferroptosis in hepatic stellate cells. Autophagy 14:2083–2103. https://doi.org/10.1080/15548627.2018.1503146
Zhao Y, Li Y, Zhang R, Wang F, Wang T, Jiao Y (2020) The role of erastin in ferroptosis and its prospects in cancer therapy. Onco Targets Ther 13:5429–5441. https://doi.org/10.2147/ott.S254995
Zheng R, Po I, Mishin V et al (2013) The generation of 4-hydroxynonenal, an electrophilic lipid peroxidation end product, in rabbit cornea organ cultures treated with UVB light and nitrogen mustard. Toxicol Appl Pharmacol 272:345–355. https://doi.org/10.1016/j.taap.2013.06.025
Zhou B, Liu J, Kang R, Klionsky DJ, Kroemer G, Tang D (2020) Ferroptosis is a type of autophagy-dependent cell death. Semin Cancer Biol 66:89–100. https://doi.org/10.1016/j.semcancer.2019.03.002
Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 82102273; No. 81971816; No. 82272208).
Author information
Authors and Affiliations
Contributions
All authors contributed to the review. Article collection and generalization were performed by [JZ], [CH] and [JJ]. The first draft of the manuscript was written by [YW] and [BW]. The figures were drawn by [BW]. The project was designed by [ZP] and [YL]. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
We declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wang, B., Wang, Y., Zhang, J. et al. ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis. Arch Toxicol 97, 1439–1451 (2023). https://doi.org/10.1007/s00204-023-03476-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-023-03476-6