Oxidative stress induces mitochondrial iron overload and ferroptotic cell death.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 09 2023
19 09 2023
Historique:
received:
10
04
2023
accepted:
14
09
2023
medline:
21
9
2023
pubmed:
20
9
2023
entrez:
19
9
2023
Statut:
epublish
Résumé
Oxidative stress has been shown to induce cell death in a wide range of human diseases including cardiac ischemia/reperfusion injury, drug induced cardiotoxicity, and heart failure. However, the mechanism of cell death induced by oxidative stress remains incompletely understood. Here we provide new evidence that oxidative stress primarily induces ferroptosis, but not apoptosis, necroptosis, or mitochondria-mediated necrosis, in cardiomyocytes. Intriguingly, oxidative stress induced by organic oxidants such as tert-butyl hydroperoxide (tBHP) and cumene hydroperoxide (CHP), but not hydrogen peroxide (H
Identifiants
pubmed: 37726294
doi: 10.1038/s41598-023-42760-4
pii: 10.1038/s41598-023-42760-4
pmc: PMC10509277
doi:
Substances chimiques
Reactive Oxygen Species
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15515Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL155035
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL160767
Pays : United States
Informations de copyright
© 2023. Springer Nature Limited.
Références
Del Re, D. P., Amgalan, D., Linkermann, A., Liu, Q. & Kitsis, R. N. Fundamental mechanisms of regulated cell death and implications for heart disease. Physiol Rev. 99, 1765–1817 (2019).
pubmed: 31364924
pmcid: 6890986
doi: 10.1152/physrev.00022.2018
Kung, G., Konstantinidis, K. & Kitsis, R. N. Programmed necrosis, not apoptosis, in the heart. Circ Res. 108, 1017–1036 (2011).
pubmed: 21493924
doi: 10.1161/CIRCRESAHA.110.225730
Edinger, A. L. & Thompson, C. B. Death by design: Apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 16, 663–669 (2004).
pubmed: 15530778
doi: 10.1016/j.ceb.2004.09.011
Cho, Y. S. et al. Phosphorylation driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137, 1112–1123 (2009).
pubmed: 19524513
pmcid: 2727676
doi: 10.1016/j.cell.2009.05.037
Zhang, D. W. et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325, 332–336 (2009).
pubmed: 19498109
doi: 10.1126/science.1172308
He, S. et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137, 1100–1011 (2009).
pubmed: 19524512
doi: 10.1016/j.cell.2009.05.021
Baines, C. P. et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434, 658–662 (2005).
pubmed: 15800627
doi: 10.1038/nature03434
Karch, J. et al. Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice. Elife 2, e00772 (2013).
pubmed: 23991283
pmcid: 3755340
doi: 10.7554/eLife.00772
Dixon, S. J. et al. Ferroptosis: An iron dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).
pubmed: 22632970
pmcid: 3367386
doi: 10.1016/j.cell.2012.03.042
Stockwell, B. R. et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171, 273–285 (2017).
pubmed: 28985560
pmcid: 5685180
doi: 10.1016/j.cell.2017.09.021
Yang, W. S. et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317–331 (2014).
pubmed: 24439385
pmcid: 4076414
doi: 10.1016/j.cell.2013.12.010
Friedmann Angeli, J. P. et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol. 16, 1180–1191 (2014).
pubmed: 25402683
doi: 10.1038/ncb3064
Papanikolaou, G. & Pantopoulos, K. Iron metabolism and toxicity. Toxicol Appl Pharmacol. 202, 199–211 (2005).
pubmed: 15629195
doi: 10.1016/j.taap.2004.06.021
Tang, D., Chen, X., Kang, R. & Kroemer, G. Ferroptosis: Molecular mechanisms and health implications. Cell Res. 31, 107–125 (2021).
pubmed: 33268902
doi: 10.1038/s41422-020-00441-1
Chen, X., Yu, C., Kang, R. & Tang, D. Iron metabolism in ferroptosis. Front Cell Dev Biol. 8, 590226 (2020).
pubmed: 33117818
pmcid: 7575751
doi: 10.3389/fcell.2020.590226
Eefting, F. et al. Role of apoptosis in reperfusion injury. Cardiovasc Res. 61, 414–426 (2004).
pubmed: 14962473
doi: 10.1016/j.cardiores.2003.12.023
Robin, E. et al. Oxidant stress during simulated ischemia primes cardiomyocytes for cell death during reperfusion. J Biol Chem. 282, 19133–19143 (2007).
pubmed: 17488710
doi: 10.1074/jbc.M701917200
Siveski-Iliskovic, N., Hill, M., Chow, D. A. & Singal, P. K. Probucol protects against adriamycin cardiomyopathy without interfering with its antitumor effect. Circulation 91, 10–15 (1995).
pubmed: 7805190
doi: 10.1161/01.CIR.91.1.10
Ludke, A., Akolkar, G., Ayyappan, P., Sharma, A. K. & Singal, P. K. Time course of changes in oxidative stress and stress-induced proteins in cardiomyocytes exposed to doxorubicin and prevention by vitamin C. PLoS ONE 12, e0179452 (2017).
pubmed: 28678856
pmcid: 5497966
doi: 10.1371/journal.pone.0179452
Kakita, T. et al. Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes. Circ Res. 88, 1239–4126 (2001).
pubmed: 11420299
doi: 10.1161/hh1201.091794
Long, X., Goldenthal, M. J., Wu, G. M. & Marín-García, J. Mitochondrial Ca2+ flux and respiratory enzyme activity decline are early events in cardiomyocyte response to H2O2. J Mol Cell Cardiol. 37, 63–70 (2004).
pubmed: 15242736
doi: 10.1016/j.yjmcc.2004.04.001
Casey, T. M., Arthur, P. G. & Bogoyevitch, M. A. Necrotic death without mitochondrial dysfunction-delayed death of cardiac myocytes following oxidative stress. Biochim Biophys Acta. 1773, 342–351 (2007).
pubmed: 17207543
doi: 10.1016/j.bbamcr.2006.11.013
Zhang, H. et al. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature 471, 373–376 (2011).
pubmed: 21368761
pmcid: 3072026
doi: 10.1038/nature09878
Vanden Berghe, T. et al. Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features. Cell Death Differ. 17, 922–930 (2010).
pubmed: 20010783
doi: 10.1038/cdd.2009.184
Zhao, W. et al. Tert-butyl hydroperoxide (t-BHP) induced apoptosis and necroptosis in endothelial cells: Roles of NOX4 and mitochondrion. Redox Biol. 11, 524–534 (2017).
pubmed: 28088644
pmcid: 5237803
doi: 10.1016/j.redox.2016.12.036
Wu, C. et al. Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells. Sci Rep. 8, 574 (2018).
pubmed: 29330409
pmcid: 5766540
doi: 10.1038/s41598-017-18935-1
Keuters, M. H. et al. An arylthiazyne derivative is a potent inhibitor of lipid peroxidation and ferroptosis providing neuroprotection in vitro and in vivo. Sci Rep. 11, 3518 (2021).
pubmed: 33568697
pmcid: 7876050
doi: 10.1038/s41598-021-81741-3
Yin, H. et al. TAB2 deficiency induces dilated cardiomyopathy by promoting RIPK1-dependent apoptosis and necroptosis. J Clin Invest. 132, e152297 (2022).
pubmed: 34990405
pmcid: 8843707
doi: 10.1172/JCI152297
Liu, Q., Busby, J. C. & Molkentin, J. D. Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signalling nodal control point. Nat Cell Biol. 11, 154–161 (2009).
pubmed: 19136967
pmcid: 2656285
doi: 10.1038/ncb1823
Guo, X. et al. TAK1 regulates caspase 8 activation and necroptotic signaling via multiple cell death checkpoints. Cell Death Dis. 7, e2381 (2016).
pubmed: 27685625
pmcid: 5059887
doi: 10.1038/cddis.2016.294
Frezza, C., Cipolat, S. & Scorrano, L. Organelle isolation: Functional mitochondria from mouse liver, muscle and cultured fibroblasts. Nat Protoc. 2, 287–295 (2007).
pubmed: 17406588
doi: 10.1038/nprot.2006.478
Yoshida, M. et al. Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis. Nat Commun. 10, 3145 (2019).
pubmed: 31316058
pmcid: 6637122
doi: 10.1038/s41467-019-10991-7
Ryter, S. W., Alam, J. & Choi, A. M. Heme oxygenase-1/carbon monoxide: From basic science to therapeutic applications. Physiol Rev. 86, 583–650 (2006).
pubmed: 16601269
doi: 10.1152/physrev.00011.2005
Suzuki, H. et al. Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene. J Biol Chem. 278, 49246–49253 (2003).
pubmed: 14504288
doi: 10.1074/jbc.M306764200
Gaschler, M. M. et al. Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis. ACS Chem Biol. 13, 1013–1020 (2018).
pubmed: 29512999
pmcid: 5960802
doi: 10.1021/acschembio.8b00199
Gao, M. et al. Role of mitochondria in ferroptosis. Mol Cell. 73, 354–363 (2019).
pubmed: 30581146
doi: 10.1016/j.molcel.2018.10.042
Oh, S. J., Ikeda, M., Ide, T., Hur, K. Y. & Lee, M. S. Mitochondrial event as an ultimate step in ferroptosis. Cell Death Discov. 8, 414 (2022).
pubmed: 36209144
pmcid: 9547870
doi: 10.1038/s41420-022-01199-8
Jelinek, A. et al. Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radic Biol Med. 117, 45–57 (2018).
pubmed: 29378335
doi: 10.1016/j.freeradbiomed.2018.01.019
Kelso, G. F. et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: Antioxidant and antiapoptotic properties. J Biol Chem. 276, 4588–4596 (2001).
pubmed: 11092892
doi: 10.1074/jbc.M009093200
Davies, M. J. Detection of peroxyl and alkoxyl radicals produced by reaction of hydroperoxides with rat liver microsomal fractions. Biochem J. 257, 603–606 (1989).
pubmed: 2930470
pmcid: 1135621
doi: 10.1042/bj2570603
Park, T. J. et al. Quantitative proteomic analyses reveal that GPX4 downregulation during myocardial infarction contributes to ferroptosis in cardiomyocytes. Cell Death Dis. 10, 835 (2019).
pubmed: 31685805
pmcid: 6828761
doi: 10.1038/s41419-019-2061-8
Tadokoro, T. et al. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight. 5, e132747 (2020).
pubmed: 32376803
pmcid: 7253028
doi: 10.1172/jci.insight.132747
Gaschler, M. M. & Stockwell, B. R. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 482, 419–425 (2017).
pubmed: 28212725
pmcid: 5319403
doi: 10.1016/j.bbrc.2016.10.086
Zhou, H. et al. NCOA4-mediated ferritinophagy is involved in ionizing radiation-induced ferroptosis of intestinal epithelial cells. Redox Biol. 55, 102413 (2022).
pubmed: 35932693
pmcid: 9356278
doi: 10.1016/j.redox.2022.102413
Garcia-Santos, D. et al. Inhibition of heme oxygenase ameliorates anemia and reduces iron overload in a β-thalassemia mouse model. Blood 131, 236–246 (2018).
pubmed: 29180398
pmcid: 5757685
doi: 10.1182/blood-2017-07-798728
Menon, A. V. et al. Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease. Blood 139, 936–941 (2022).
pubmed: 34388243
pmcid: 8832481
doi: 10.1182/blood.2020008455
Fang, X. et al. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci U S A. 116, 2672–2680 (2019).
pubmed: 30692261
pmcid: 6377499
doi: 10.1073/pnas.1821022116
Hui, Y. et al. Long-term overexpression of heme oxygenase 1 promotes tau aggregation in mouse brain by inducing tau phosphorylation. J Alzheimers Dis. 26, 299–313 (2011).
pubmed: 21613741
doi: 10.3233/JAD-2011-102061
Wang, G. et al. Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart. Circulation 121, 1912–1925 (2010).
pubmed: 20404253
pmcid: 2917269
doi: 10.1161/CIRCULATIONAHA.109.905471
Chiang, S. K., Chen, S. E. & Chang, L. C. A dual role of heme oxygenase-1 in cancer cells. Int J Mol Sci. 20, 39 (2018).
pubmed: 30583467
pmcid: 6337503
doi: 10.3390/ijms20010039
Miyamoto, H. D. et al. Iron overload via heme degradation in the endoplasmic reticulum triggers ferroptosis in myocardial ischemia-reperfusion injury. JACC Basic Transl Sci. 7, 800–819 (2022).
pubmed: 36061338
pmcid: 9436815
doi: 10.1016/j.jacbts.2022.03.012
Shan, Y., Lambrecht, R. W., Donohue, S. E. & Bonkovsky, H. L. Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin. FASEB J. 20, 2651–2653 (2006).
pubmed: 17065227
doi: 10.1096/fj.06-6346fje
Reichard, J. F., Motz, G. T. & Puga, A. Heme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1. Nucleic Acids Res. 35, 7074–7086 (2007).
pubmed: 17942419
pmcid: 2175339
doi: 10.1093/nar/gkm638
Sardão, V. A., Oliveira, P. J., Holy, J., Oliveira, C. R. & Wallace, K. B. Vital imaging of H9c2 myoblasts exposed to tert-butylhydroperoxide–characterization of morphological features of cell death. BMC Cell Biol. 8, 11 (2007).
pubmed: 17362523
pmcid: 1831770
doi: 10.1186/1471-2121-8-11
Guo, L. Mitochondrial ATP synthase inhibitory factor 1 interacts with the p53-cyclophilin D complex and promotes opening of the permeability transition pore. J Biol Chem. 298, 101858 (2022).
pubmed: 35337801
pmcid: 9043413
doi: 10.1016/j.jbc.2022.101858
Bansal, S., Biswas, G. & Avadhani, N. G. Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity. Redox Biol. 2, 273–283 (2013).
pubmed: 24494190
pmcid: 3909819
doi: 10.1016/j.redox.2013.07.004
Mao, C. et al. DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer. Nature 593, 586–590 (2021).
pubmed: 33981038
pmcid: 8895686
doi: 10.1038/s41586-021-03539-7
Ichikawa, Y. et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest. 124, 617–630 (2014).
pubmed: 24382354
pmcid: 3904631
doi: 10.1172/JCI72931
Paradkar, P. N., Zumbrennen, K. B., Paw, B. H., Ward, D. M. & Kaplan, J. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol Cell Biol. 29, 1007–1016 (2009).
pubmed: 19075006
doi: 10.1128/MCB.01685-08
Hung, H. I., Schwartz, J. M., Maldonado, E. N., Lemasters, J. J. & Nieminen, A. L. Mitoferrin-2-dependent mitochondrial iron uptake sensitizes human head and neck squamous carcinoma cells to photodynamic therapy. J Biol Chem. 288, 677–686 (2013).
pubmed: 23135267
doi: 10.1074/jbc.M112.422667
Chang, H. C. et al. Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med. 8, 247–267 (2016).
pubmed: 26896449
pmcid: 4772952
doi: 10.15252/emmm.201505748
Kumar, V. et al. Chronic pressure overload results in deficiency of mitochondrial membrane transporter ABCB7 which contributes to iron overload, mitochondrial dysfunction, metabolic shift and worsens cardiac function. Sci Rep. 9, 13170 (2019).
pubmed: 31511561
pmcid: 6739357
doi: 10.1038/s41598-019-49666-0