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Ferroptosis is a novel form of regulated cell death characterized by iron-dependent excessive lipid peroxidation. The core organelle involved in ferroptosis is mitochondria. Mitochondria undergoing ferroptosis are distinct from normal mitochondria in terms of morphology, biochemistry, gene expression, and energy metabolism. An increasing number of studies have shown that mitochondria and their associated metabolic pathways mediate ferroptosis in the development and progression of breast cancer. In this review, we discuss the relevant research about ferroptosis in breast cancer and provide a comprehensive summary of mitochondrial regulation in ferroptosis from the perspective of lipid metabolism, oxidative phosphorylation, ion metabolism, glycometabolism, and nucleotide metabolism. We also summarize the application of mitochondrial metabolism-related pathways as ferroptosis treatment targets. Here we provide new insights into the relationship between mitochondria, ferroptosis, and breast cancer treatment.
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060-1072.
Chen X, Kang R, Kroemer G, et al. Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol. 2021;18(5):280-296.
Bogdan AR, Miyazawa M, Hashimoto K, et al. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci. 2016;41(3):274-286.
Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol. 2017;13(1):91-98.
Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273-285.
Tang D, Kroemer G. Ferroptosis. Curr Biol. 2020;30(21):R1292-R1297.
Handy DE, Loscalzo J. Redox regulation of mitochondrial function. Antioxidants Redox Signal. 2012;16(11):1323-1367.
Sato H, Tamba M, Ishii T, et al. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J Biol Chem. 1999;274(17):11455-11458.
Meister A. Glutathione metabolism. Methods Enzymol. 1995;251:3-7.
Seiler A, Schneider M, Förster H, et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metabol. 2008;8(3):237-248.
de Jong G, van Dijk JP, van Eijk HG. The biology of transferrin. Clin Chim Acta. 1990;190(1-2):1-46.
Tang Z, Zhao P, Wang H, et al. Biomedicine meets Fenton chemistry. Chem Rev. 2021;121(4):1981-2019.
Conrad M, Pratt DA. The chemical basis of ferroptosis. Nat Chem Biol. 2019;15(12):1137-1147.
Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909-950.
Shen Z, Song J, Yung BC, et al. Emerging strategies of cancer therapy based on ferroptosis. Adv Mater. 2018;30(12):e1704007.
Su LJ, Zhang JH, Gomez H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019;2019:5080843.
Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation. Trends Cell Biol. 2016;26(3):165-176.
Bao WD, Pang P, Zhou XT, et al. Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease. Cell Death Differ. 2021;28(5):1548-1562.
Fang X, Cai Z, Wang H, et al. Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ Res. 2020;127(4):486-501.
Stockwell BR, Jiang X, Gu W. Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol. 2020;30(6):478-490.
Lill R, Freibert SA. Mechanisms of mitochondrial iron-sulfur protein biogenesis. Annu Rev Biochem. 2020;89:471-499.
Speijer D. Oxygen radicals shaping evolution: why fatty acid catabolism leads to peroxisomes while neurons do without it: FADH2/NADH flux ratios determining mitochondrial radical formation were crucial for the eukaryotic invention of peroxisomes and catabolic tissue differentiation. Bioessays. 2011;33(2):88-94.
Hunt MC, Tillander V, Alexson SEH. Regulation of peroxisomal lipid metabolism: the role of acyl-CoA and coenzyme A metabolizing enzymes. Biochimie. 2014;98:45-55.
Tesfay L, Paul BT, Konstorum A, et al. Stearoyl-CoA desaturase 1 protects ovarian cancer cells from ferroptotic cell death. Cancer Res. 2019;79(20):5355-5366.
Brash AR. Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem. 1999;274(34):23679-23682.
Pallast S, Arai K, Wang X, et al. 12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress. J Neurochem. 2009;111(3):882-889.
Stoyanovsky DA, Tyurina YY, Shrivastava I, et al. Iron catalysis of lipid peroxidation in ferroptosis: regulated enzymatic or random free radical reaction? Free Radic Biol Med. 2019;133:153-161.
Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol. 2017;13(1):81-90.
Magtanong L, Ko PJ, To M, et al. Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem Biol. 2019;26(3):420-432.e9.
Miess H, Dankworth B, Gouw AM, et al. The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma. Oncogene. 2018;37(40):5435-5450.
Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1-13.
Gao M, Yi J, Zhu J, et al. Role of mitochondria in ferroptosis. Mol Cell. 2019;73(2):354-363.e3.
Shimada K, Hayano M, Pagano N, et al. Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity. Cell Chem Biol. 2016;23(2):225-235.
Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019;575(7784):688-692.
Doll S, Freitas FP, Shah R, et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019;575(7784):693-698.
Kanzok SM, Fechner A, Bauer H, et al. Substitution of the thioredoxin system for glutathione reductase in Drosophila melanogaster. Science. 2001;291(5504):643-646.
Wu H, Wang F, Ta N, et al. The multifaceted regulation of mitochondria in ferroptosis. Life. 2021;11(3):222.
Douda DN, Khan MA, Grasemann H, et al. SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx. Proc Natl Acad Sci U S A. 2015;112(9):2817-2822.
DeHart DN, Fang D, Heslop K, et al. Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells. Biochem Pharmacol. 2018;148:155-162.
Gao M, Monian P, Quadri N, et al. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 2015;59(2):298-308.
Mon EE, Wei FY, Ahmad RNR, et al. Regulation of mitochondrial iron homeostasis by sideroflexin 2. J Physiol Sci. 2019;69(2):359-373.
Fang X, Wang H, Han D, et al. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci U S A. 2019;116(7):2672-2680.
Gao G, Chang YZ. Mitochondrial ferritin in the regulation of brain iron homeostasis and neurodegenerative diseases. Front Pharmacol. 2014;5:19.
Zecca L, Youdim MBH, Riederer P, et al. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004;5(11):863-873.
Gleitze S, Paula-Lima A, Núñez MT, et al. The calcium-iron connection in ferroptosis-mediated neuronal death. Free Radic Biol Med. 2021;175:28-41.
Núñez MT, Hidalgo C. Noxious iron-calcium connections in neurodegeneration. Front Neurosci. 2019;13:48.
Görlach A, Bertram K, Hudecova S, et al. Calcium and ROS: a mutual interplay. Redox Biol. 2015;6:260-271.
Lipper CH, Karmi O, Sohn YS, et al. Structure of the human monomeric NEET protein MiNT and its role in regulating iron and reactive oxygen species in cancer cells. Proc Natl Acad Sci U S A. 2018;115(2):272-277.
Do Van B, Gouel F, Jonneaux A, et al. Ferroptosis, a newly characterized form of cell death in Parkinson’s disease that is regulated by PKC. Neurobiol Dis. 2016;94:169-178.
Santambrogio P, Ripamonti M, Paolizzi C, et al. Harmful iron-calcium relationship in pantothenate kinase associated neurodegeneration. Int J Mol Sci. 2020;21(10):3664.
Wang X, Lu S, He C, et al. RSL3 induced autophagic death in glioma cells via causing glycolysis dysfunction. Biochem Biophys Res Commun. 2019;518(3):590-597.
Gincel D, Silberberg SD, Shoshan-Barmatz V. Modulation of the voltage-dependent anion channel (VDAC) by Glutamate1. J Bioenerg Biomembr. 2000;32(6):571-583.
Rostovtseva T, Colombini M. VDAC channels mediate and gate the flow of ATP: implications for the regulation of mitochondrial function. Biophys J. 1997;72(5):1954-1962.
Kang W, Suzuki M, Saito T, et al. Emerging role of TCA cycle-related enzymes in human diseases. Int J Mol Sci. 2021;22(23):13057.
DeBerardinis RJ, Mancuso A, Daikhin E, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci U S A. 2007;104(49):19345-19350.
Lee H, Zandkarimi F, Zhang Y, et al. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol. 2020;22(2):225-234.
Guo J, Duan L, He X, et al. A combined model of human iPSC-derived liver organoids and hepatocytes reveals ferroptosis in DGUOK mutant mtDNA depletion syndrome. Adv Sci 2021;8(10):2004680.
Li C, Zhang Y, Liu J, et al. Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. Autophagy. 2021;17(4):948-960.
Toyokuni S, Ito F, Yamashita K, et al. Iron and thiol redox signaling in cancer: an exquisite balance to escape ferroptosis. Free Radic Biol Med. 2017;108:610-626.
Brown CW, Amante JJ, Goel HL, et al. The α6β4 integrin promotes resistance to ferroptosis. J Cell Biol. 2017;216(12):4287-4297.
Yang F, Xiao Y, Ding JH, et al. Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy. Cell Metabol. 2023;35(1):84-100.e8.
Dattilo MA, Benzo Y, Herrera LM, et al. Regulatory mechanisms leading to differential Acyl-CoA synthetase 4 expression in breast cancer cells. Sci Rep. 2019;9:10324.
Sarmiento-Salinas FL, Delgado-Magallón A, Montes-Alvarado JB, et al. Breast cancer subtypes present a differential production of reactive oxygen species (ROS) and susceptibility to antioxidant treatment. Front Oncol. 2019;9:480.
Müller S, Sindikubwabo F, Cañeque T, et al. CD44 regulates epigenetic plasticity by mediating iron endocytosis. Nat Chem. 2020;12(10):929-938.
Liu W, Chakraborty B, Safi R, et al. Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nat Commun. 2021;12:5103.
Li H, Yang P, Wang J, et al. HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk. J Hematol Oncol. 2022;15:2.
Li Z, Chen L, Chen C, et al. Targeting ferroptosis in breast cancer. Biomark Res. 2020;8:58.
Ding Y, Chen X, Liu C, et al. Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells. J Hematol Oncol. 2021;14:19.
Luis G, Godfroid A, Nishiumi S, et al. Tumor resistance to ferroptosis driven by stearoyl-CoA desaturase-1 (SCD1) in cancer cells and fatty acid binding protein-4 (FABP4) in tumor microenvironment promote tumor recurrence. Redox Biol. 2021;43:102006.
Sun L, Wang H, Yu S, et al. Herceptin induces ferroptosis and mitochondrial dysfunction in H9c2 cells. Int J Mol Med. 2022;49(2):17.
MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999;366(1):82-88.
Hart PC, Mao M, de Abreu ALP, et al. MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer. Nat Commun. 2015;6:6053.
Ma S, Fu X, Liu L, et al. Iron-dependent autophagic cell death induced by radiation in MDA-MB-231 breast cancer cells. Front Cell Dev Biol. 2021;9:723801.
Wu CW, Yin PH, Hung WY, et al. Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosomes Cancer. 2005;44(1):19-28.
Nie H, Chen G, He J, et al. Mitochondrial common deletion is elevated in blood of breast cancer patients mediated by oxidative stress. Mitochondrion. 2016;26:104-112.
Sui S, Xu S, Pang D. Emerging role of ferroptosis in breast cancer: new dawn for overcoming tumor progression. Pharmacol Ther. 2022;232:107992.
Sohn YS, Tamir S, Song L, et al. NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proc Natl Acad Sci U S A. 2013;110(36):14676-14681.
Bai F, Morcos F, Sohn YS, et al. The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer. Proc Natl Acad Sci U S A. 2015;112(12):3698-3703.
Louandre C, Ezzoukhry Z, Godin C, et al. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int J Cancer. 2013;133(7):1732-1742.
Sang M, Luo R, Bai Y, et al. Mitochondrial membrane anchored photosensitive nano-device for lipid hydroperoxides burst and inducing ferroptosis to surmount therapy-resistant cancer. Theranostics. 2019;9(21):6209-6223.
Yao X, Xie R, Cao Y, et al. Simvastatin induced ferroptosis for triple-negative breast cancer therapy. J Nanobiotechnol. 2021;19:311.
Li K, Lin C, Li M, et al. Multienzyme-like reactivity cooperatively impairs glutathione peroxidase 4 and ferroptosis suppressor protein 1 pathways in triple-negative breast cancer for sensitized ferroptosis therapy. ACS Nano. 2022;16(2):2381-2398.
Zou Y, Xie J, Zheng S, et al. Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery. Int J Surg. 2022;107:106936.
Sha R, Xu Y, Yuan C, et al. Predictive and prognostic impact of ferroptosis-related genes ACSL4 and GPX4 on breast cancer treated with neoadjuvant chemotherapy. EBioMedicine. 2021;71:103560.
Song X, Wang X, Liu Z, et al. Role of GPX4-mediated ferroptosis in the sensitivity of triple negative breast cancer cells to gefitinib. Front Oncol. 2020;10:597434.
Turcu AL, Versini A, Khene N, et al. DMT1 inhibitors kill cancer stem cells by blocking lysosomal iron translocation. Chemistry. 2020;26(33):7369-7373.
Zou Y, Zheng S, Xie X, et al. N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022;13:2672.
Eaton JK, Furst L, Ruberto RA, et al. Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles. Nat Chem Biol. 2020;16(5):497-506.
Zou Y, Schreiber SL. Progress in understanding ferroptosis and challenges in its targeting for therapeutic benefit. Cell Chem Biol. 2020;27(4):463-471.
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