Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration

Moataz Abdalkader1, Riikka Lampinen1, Katja M. Kanninen1, Tarja Malm1, Jeffrey R. Liddell2
1A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland
2Department of Pharmacology and Therapeutics, The University of Melbourne, Australia

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Abeysinghe, 1996, The environment of the lipoxygenase iron binding site explored with novel hydroxypyridinone iron chelators., J. Biol. Chem., 271, 7965, 10.1074/jbc.271.14.7965

Adibhatla, 2010, Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities., Antioxid. Redox Signal., 12, 125, 10.1089/ars.2009.2668

Agyeman, 2012, Transcriptomic and proteomic profiling of KEAP1 disrupted and sulforaphane-treated human breast epithelial cells reveals common expression profiles., Breast Cancer Res. Treat., 132, 175, 10.1007/s10549-011-1536-9

Alam, 1999, Nrf2, a Cap‘n’Collar transcription factor, regulates induction of the heme oxygenase-1 gene., J. Biol. Chem., 274, 26071, 10.1074/jbc.274.37.26071

Ayton, 2017, Cerebral quantitative susceptibility mapping predicts amyloid-beta-related cognitive decline., Brain, 140, 2112, 10.1093/brain/awx137

Ayton, 2014, Nigral iron elevation is an invariable feature of Parkinson’s disease and is a sufficient cause of neurodegeneration., BioMed Res. Int., 2014, 10.1155/2014/581256

Basit, 2017, Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells., Cell Death Dis., 8, 10.1038/cddis.2017.133

Belaidi, 2016, Iron neurochemistry in Alzheimer’s disease and Parkinson’s disease: targets for therapeutics., J. Neurochem., 139, 179, 10.1111/jnc.13425

Bradley-Whitman, 2015, Biomarkers of lipid peroxidation in Alzheimer disease (AD): an update., Arch. Toxicol., 89, 1035, 10.1007/s00204-015-1517-6

Cai, 2017, Peroxisome proliferator-activated receptor gamma (PPARgamma): a master gatekeeper in CNS injury and repair., Prog. Neurobiol., 27, 10.1016/j.pneurobio.2017.10.002

Campbell, 2013, Novel hematopoietic target genes in the NRF2-mediated transcriptional pathway., Oxid. Med. Cell. Longev., 2013, 10.1155/2013/120305

Carri, 2017, Pathways to mitochondrial dysfunction in ALS pathogenesis., Biochem. Biophys. Res. Commun., 483, 1187, 10.1016/j.bbrc.2016.07.055

Chen, , The oxido-metabolic driver ATF4 enhances temozolamide chemo-resistance in human gliomas., Oncotarget, 8, 51164, 10.18632/oncotarget.17737

Chen, , NRF2 is a major target of ARF in p53-independent tumor suppression., Mol. Cell, 68, 224, 10.1016/j.molcel.2017.09.009

Chen, 2015, Ablation of the ferroptosis inhibitor glutathione peroxidase 4 in neurons results in rapid motor neuron degeneration and paralysis., J. Biol. Chem., 290, 28097, 10.1074/jbc.M115.680090

Cho, 2010, Nrf2-regulated PPAR{gamma} expression is critical to protection against acute lung injury in mice., Am. J. Res. Crit. Care Med., 182, 170, 10.1164/rccm.200907-1047OC

Cozzolino, 2012, Mitochondrial dysfunction in ALS., Prog. Neurobiol., 97, 54, 10.1016/j.pneurobio.2011.06.003

Crapper McLachlan, 1991, Intramuscular desferrioxamine in patients with Alzheimer’s disease., Lancet, 337, 1304, 10.1016/0140-6736(91)92978-B

Devos, 2014, Targeting chelatable iron as a therapeutic modality in Parkinson’s disease., Antioxid. Redox Signal., 21, 195, 10.1089/ars.2013.5593

Dinkova-Kostova, 2015, The emerging role of Nrf2 in mitochondrial function., Free Radic. Biol. Med., 88, 179, 10.1016/j.freeradbiomed.2015.04.036

Dixon, 2012, Ferroptosis: an iron-dependent form of nonapoptotic cell death., Cell, 149, 1060, 10.1016/j.cell.2012.03.042

Dixon, 2015, Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death., ACS Chem. Biol., 10, 1604, 10.1021/acschembio.5b00245

Do Van, 2016, Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC., Neurobiol. Dis., 94, 169, 10.1016/j.nbd.2016.05.011

Doll, 2017, ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition., Nat. Chem. Biol., 13, 91, 10.1038/nchembio.2239

East, 2014, PMI: a DeltaPsim independent pharmacological regulator of mitophagy., Chem. Biol., 21, 1585, 10.1016/j.chembiol.2014.09.019

Fan, 2017, Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis., Oncogenesis, 6, 10.1038/oncsis.2017.65

Fricker, 2018, Neuronal cell death., Physiol. Rev., 98, 813, 10.1152/physrev.00011.2017

Friedmann Angeli, 2014, Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice., Nat. Cell Biol., 16, 1180, 10.1038/ncb3064

Galluzzi, 2018, Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018., Cell Death Differ., 25, 486, 10.1038/s41418-017-0012-4

Gao, 2014, The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders., Clin. Pharmacol., 6, 19

Gaschler, 2018, Determination of the subcellular localization and mechanism of action of ferrostatins in suppressing ferroptosis., ACS Chem. Biol., 13, 1013, 10.1021/acschembio.8b00199

Greco, 2010, Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition., J. Bioenerg. Biomembr., 42, 491, 10.1007/s10863-010-9312-9

Guiney, 2017, Ferroptosis and cell death mechanisms in Parkinson’s disease., Neurochem. Int., 104, 34, 10.1016/j.neuint.2017.01.004

Hambright, 2017, Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration., Redox Biol., 12, 8, 10.1016/j.redox.2017.01.021

Havrdova, 2017, Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies., Eur. J. Neurol., 24, 726, 10.1111/ene.13272

Holmstrom, 2016, The multifaceted role of Nrf2 in mitochondrial function., Curr. Opin. Toxicol., 1, 80, 10.1016/j.cotox.2016.10.002

Houessinon, 2016, Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib., Mol. Cancer, 15, 10.1186/s12943-016-0526-2

Hu, 2018, The mitochondrially targeted antioxidant MitoQ protects the intestinal barrier by ameliorating mitochondrial DNA damage via the Nrf2/ARE signaling pathway., Cell Death Dis., 9, 10.1038/s41419-018-0436-x

Imai, 2003, Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene., Biochem. Biophys. Res. Commun., 305, 278, 10.1016/S0006-291X(03)00734-4

Ingold, 2018, Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis., Cell, 172, e421, 10.1016/j.cell.2017.11.048

Itoh, 2008, Structural basis for the activation of PPARgamma by oxidized fatty acids., Nat. Struct. Mol. Biol., 15, 924, 10.1038/nsmb.1474

Jaarsma, 2000, Human Cu/Zn superoxide dismutase (SOD1) overexpression in mice causes mitochondrial vacuolization, axonal degeneration, and premature motoneuron death and accelerates motoneuron disease in mice expressing a familial amyotrophic lateral sclerosis mutant SOD1., Neurobiol. Dis., 7, 623, 10.1006/nbdi.2000.0299

Jelinek, 2018, Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis., Free Radic. Biol. Med., 117, 45, 10.1016/j.freeradbiomed.2018.01.019

Kagan, 2017, Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis., Nat. Chem. Biol., 13, 81, 10.1038/nchembio.2238

Kerins, 2017, The roles of NRF2 in modulating cellular iron homeostasis., Antioxid. Redox Signal., 10.1089/ars.2017.7176

Krainz, 2016, A mitochondrial-targeted nitroxide is a potent inhibitor of ferroptosis., ACS Cent. Sci., 2, 653, 10.1021/acscentsci.6b00199

Kwak, 2003, Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival., J. Biol. Chem., 278, 8135, 10.1074/jbc.M211898200

Kwan, 2012, Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology., PLoS One, 7, 10.1371/journal.pone.0035241

Lee, 2017, Collaborative power of Nrf2 and PPARgamma activators against metabolic and drug-induced oxidative injury., Oxid. Med. Cell. Longev., 2017, 10.1155/2017/1378175

Lee, 2011, Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington’s disease mice., Acta Neuropathol., 121, 487, 10.1007/s00401-010-0788-5

Lee, 2003, Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis., J. Biol. Chem., 278, 12029, 10.1074/jbc.M211558200

Lewerenz, 2018, Oxytosis/ferroptosis-(Re-) emerging roles for oxidative stress-dependent non-apoptotic cell death in diseases of the central nervous system., Front. Neurosci., 12, 10.3389/fnins.2018.00214

Li, 2016, Role of iron in neurodegenerative diseases., J. Neural Transm., 123, 389, 10.1007/s00702-016-1508-7

Li, 2017, Inhibition of neuronal ferroptosis protects hemorrhagic brain., JCI Insight, 2, 10.1172/jci.insight.90777

Liddell, 2017, Are astrocytes the predominant cell type for activation of Nrf2 in aging and neurodegeneration?, Antioxidants, 6, 10.3390/antiox6030065

Liddell, 2017, Nexus between mitochondrial function, iron, copper and glutathione in Parkinson’s disease., Neurochem. Int., 117, 126, 10.1016/j.neuint.2017.05.016

Liot, 2017, Energy defects in Huntington’s disease: why “in vivo” evidence matters., Biochem. Biophys. Res. Commun., 483, 1084, 10.1016/j.bbrc.2016.09.065

Liu, 2015, The 5-lipoxygenase inhibitor zileuton confers neuroprotection against glutamate oxidative damage by inhibiting ferroptosis., Biol. Pharm. Bull., 38, 1234, 10.1248/bpb.b15-00048

Lo, 2008, PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria., Exp. Cell Res., 314, 1789, 10.1016/j.yexcr.2008.02.014

Maiorino, 2017, GPx4 lipid peroxidation, and cell death: discoveries, rediscoveries, and open issues., Antioxid. Redox Signal., 29, 61, 10.1089/ars.2017.7115

Marro, 2010, Heme controls ferroportin1 (FPN1) transcription involving Bach1, Nrf2 and a MARE/ARE sequence motif at position -7007 of the FPN1 promoter., Haematologica, 95, 1261, 10.3324/haematol.2009.020123

Merry, 2016, Nuclear factor erythroid-derived 2-like 2 (NFE2L2, Nrf2) mediates exercise-induced mitochondrial biogenesis and the anti-oxidant response in mice., J. Physiol., 594, 5195, 10.1113/JP271957

Mittler, 2018, NEET proteins: a new link between iron metabolism, ROS and cancer., Antioxid. Redox Signal., 10.1089/ars.2018.7502

Morris, 2018, Why should neuroscientists worry about iron? The emerging role of ferroptosis in the pathophysiology of neuroprogressive diseases., Behav. Brain Res., 341, 154, 10.1016/j.bbr.2017.12.036

Moujalled, 2017, TDP-43 mutations causing amyotrophic lateral sclerosis are associated with altered expression of RNA-binding protein hnRNP K and affect the Nrf2 antioxidant pathway., Hum. Mol. Genet., 26, 1732, 10.1093/hmg/ddx093

Navarro, 2017, Heme-Oxygenase I and PCG-1alpha regulate mitochondrial biogenesis via microglial activation of alpha7 nicotinic acetylcholine receptors using PNU282987., Antioxid. Redox Signal., 27, 93, 10.1089/ars.2016.6698

Neitemeier, 2017, BID links ferroptosis to mitochondrial cell death pathways., Redox Biol., 12, 558, 10.1016/j.redox.2017.03.007

Neymotin, 2011, Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis., Free Radic. Biol. Med., 51, 88, 10.1016/j.freeradbiomed.2011.03.027

Piantadosi, 2008, Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1., Circ. Res., 103, 1232, 10.1161/01.RES.0000338597.71702.ad

Pietsch, 2003, Nrf2 mediates the induction of ferritin H in response to xenobiotics and cancer chemopreventive dithiolethiones., J. Biol. Chem., 278, 2361, 10.1074/jbc.M210664200

Roh, 2017, Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis., Redox Biol., 11, 254, 10.1016/j.redox.2016.12.010

Salazar, 2006, Glycogen synthase kinase-3beta inhibits the xenobiotic and antioxidant cell response by direct phosphorylation and nuclear exclusion of the transcription factor Nrf2., J. Biol. Chem., 281, 14841, 10.1074/jbc.M513737200

Sasaki, 2002, Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression., J. Biol. Chem., 277, 44765, 10.1074/jbc.M208704200

Seiler, 2008, Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death., Cell Metab., 8, 237, 10.1016/j.cmet.2008.07.005

Shah, 2017, Resolving the role of lipoxygenases in the initiation and execution of ferroptosis., ACS Cent. Sci., 4, 387, 10.1021/acscentsci.7b00589

Sheykhansari, 2018, Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review., Cell Death Dis., 9, 10.1038/s41419-018-0379-2

Shichiri, 2014, The role of lipid peroxidation in neurological disorders., J. Clin. Biochem. Nutr., 54, 151, 10.3164/jcbn.14-10

Skouta, 2014, Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models., J. Am. Chem. Soc., 136, 4551, 10.1021/ja411006a

Smith, 2010, Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment., J. Alzheimers Dis., 19, 363, 10.3233/JAD-2010-1239

Stockwell, 2017, Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease., Cell, 171, 273, 10.1016/j.cell.2017.09.021

Sugiyama, 2014, Immunochemical detection of lipid hydroperoxide- and aldehyde-modified proteins in diseases., Subcell. Biochem., 77, 115, 10.1007/978-94-007-7920-4_10

Sun, , Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis., Hepatology, 64, 488, 10.1002/hep.28574

Sun, , Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells., Hepatology, 63, 173, 10.1002/hep.28251

Swerdlow, 2017, Mitochondria and mitochondrial cascades in Alzheimer’s disease., J. Alzheimers Dis., 62, 1403, 10.3233/JAD-170585

Taguchi, 2017, The KEAP1-NRF2 system in cancer., Front. Oncol., 7, 10.3389/fonc.2017.00085

Tan, 2001, Oxytosis: a novel form of programmed cell death., Curr. Top. Med. Chem., 1, 497, 10.2174/1568026013394741

Thimmulappa, 2002, Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray., Cancer Res., 62, 5196

Tuo, 2017, Tau-mediated iron export prevents ferroptotic damage after ischemic stroke., Mol. Psychiatry, 22, 1520, 10.1038/mp.2017.171

Ueta, 2012, Glutathione peroxidase 4 is required for maturation of photoreceptor cells., J. Biol. Chem., 287, 7675, 10.1074/jbc.M111.335174

Vargas, 2011, Decreased glutathione accelerates neurological deficit and mitochondrial pathology in familial ALS-linked hSOD1(G93A) mice model., Neurobiol. Dis., 43, 543, 10.1016/j.nbd.2011.04.025

Wang, 2014, Oxidative stress induced by lipid peroxidation is related with inflammation of demyelination and neurodegeneration in multiple sclerosis., Eur. Neurol., 72, 249, 10.1159/000363515

Wang, 2016, The protective role of mitochondrial ferritin on erastin-induced ferroptosis., Front. Aging Neurosci., 8, 10.3389/fnagi.2016.00308

Wu, 2011, Beneficial role of Nrf2 in regulating NADPH generation and consumption., Toxicol. Sci., 123, 590, 10.1093/toxsci/kfr183

Xu, 2007, Necrostatin-1 protects against glutamate-induced glutathione depletion and caspase-independent cell death in HT-22 cells., J. Neurochem., 103, 2004, 10.1111/j.1471-4159.2007.04884.x

Xu, 2010, The role of PARP activation in glutamate-induced necroptosis in HT-22 cells., Brain Res., 1343, 206, 10.1016/j.brainres.2010.04.080

Yagoda, 2007, RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels., Nature, 447, 864, 10.1038/nature05859

Yamamoto, 2018, The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis., Physiol. Rev., 98, 1169, 10.1152/physrev.00023.2017

Yang, 2016, Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis., Proc. Natl. Acad. Sci. U.S.A., 113, E4966, 10.1073/pnas.1603244113

Yang, 2014, Regulation of ferroptotic cancer cell death by GPX4., Cell, 156, 317, 10.1016/j.cell.2013.12.010

Yoo, 2012, Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain., Free Radic. Biol. Med., 52, 1820, 10.1016/j.freeradbiomed.2012.02.043

Yuan, , CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation., Biochem. Biophys. Res. Commun., 478, 838, 10.1016/j.bbrc.2016.08.034

Yuan, , Identification of ACSL4 as a biomarker and contributor of ferroptosis., Biochem. Biophys. Res. Commun., 478, 1338, 10.1016/j.bbrc.2016.08.124

Zille, 2017, Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis., Stroke, 48, 1033, 10.1161/STROKEAHA.116.015609