Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-14T05:21:28.831Z Has data issue: false hasContentIssue false
  • English
  • Français

Ferroptosis Regulation by Nutrient Signalling

Published online by Cambridge University Press:  08 July 2021

Yingao Qi ,
Xiaoli Zhang ,
Zhihui Wu ,
Min Tian ,
Fang Chen ,
Wutai Guan  and
Shihai Zhang Open the ORCID record for Shihai Zhang [Opens in a new window]
Yingao Qi
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
Xiaoli Zhang
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
Zhihui Wu
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
Min Tian
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
Fang Chen
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou510642, China
Wutai Guan*
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou510642, China
Shihai Zhang*
Affiliation:
Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou510642, China Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States
*
*Correspondence: Wutai Guan, email: [email protected]; Shihai Zhang, Email: [email protected]
*Correspondence: Wutai Guan, email: [email protected]; Shihai Zhang, Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Tremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases.

Keywords

Nutrient sensingSeFeAMPKmTORC1Ferroptosis
Type
Review Article
Information
Nutrition Research Reviews , Volume 35 , Issue 2 , December 2022 , pp. 282 - 294
Check for updates
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Dixon, SJ, Lemberg, KM, Lamprecht, MR et al. (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072.CrossRefGoogle ScholarPubMed
Yagoda, N, von Rechenberg, M, Zaganjor, E et al. (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447, 864–868.CrossRefGoogle ScholarPubMed
Yang, WS, SriRamaratnam, R, Welsch, ME et al. (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317–331.CrossRefGoogle ScholarPubMed
Conrad, M, Pratt, DA (2019) The chemical basis of ferroptosis. Nat Chem Biol 15, 1137–1147.CrossRefGoogle ScholarPubMed
Gaschler, MM, Stockwell, BR (2017) Lipid peroxidation in cell death. Biochem Biophys Res Commun 482, 419–425.CrossRefGoogle ScholarPubMed
Kuhn, H, Banthiya, S, Van Leyen, K (2015) Mammalian lipoxygenases and their biological relevance. Biochim Biophys Acta Mol Cell Biol Lipids 1851, 308–330.CrossRefGoogle ScholarPubMed
Li, Y, Maher, P, Schubert, D (1997) A role for 12-lipoxygenase in nerve cell death caused by glutathione depletion. Neuron 19, 453–463.CrossRefGoogle ScholarPubMed
Zou, Y, Li, H, Graham, ET et al. (2020) Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol 16, 302–309.CrossRefGoogle ScholarPubMed
Ghosh, MK, Mukhopadhyay, M, Chatterjee, IB (1997) NADPH-initiated cytochrome P450-dependent free iron-independent microsomal lipid peroxidation: specific prevention by ascorbic acid. Mol Cell Biochem 166, 35–44.CrossRefGoogle ScholarPubMed
Doll, S, Freitas, FP, Shah, R et al. (2019) FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693–698.CrossRefGoogle ScholarPubMed
Bersuker, K, Hendricks, JM, Li, Z et al. (2019) The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688–692.CrossRefGoogle ScholarPubMed
Abbaspour, N, Hurrell, R, Kelishadi, R (2014) Review on iron and its importance for human health. J Res Med Sci 19, 164.Google ScholarPubMed
Dary, O, Hurrell, R (2006) Guidelines on food fortification with micronutrients. World Health Organization, Food and Agricultural Organization of the United Nations: Geneva, Switzerland, 1–376.Google Scholar
Yang, WS, Kim, KJ, Gaschler, MM et al. (2016) Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci 113, E4966–E4975.CrossRefGoogle ScholarPubMed
Yu, Y, Jiang, L, Wang, H et al. (2020) Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis. Blood J Am Soc Hematol 136, 726–739.Google Scholar
Brown, CW, Amante, JJ, Chhoy, P et al. (2019) Prominin2 drives ferroptosis resistance by stimulating iron export. Dev Cell 51, 575–586. e574.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Alvarez, SW, Sviderskiy, VO, Terzi, EM et al. (2017) NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature 551, 639–643.CrossRefGoogle ScholarPubMed
Du, J, Wang, T, Li, Y et al. (2019) DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. Free Radic Biol Med 131, 356–369.CrossRefGoogle ScholarPubMed
Yuan, H, Li, X, Zhang, X et al. (2016) CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys Res Commun 478, 838–844.CrossRefGoogle ScholarPubMed
Kim, EH, Shin, D, Lee, J et al. (2018) CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer. Cancer Lett 432, 180–190.CrossRefGoogle ScholarPubMed
Chen, X, Yu, C, Kang, R et al. (2020) Iron metabolism in ferroptosis. Front Cell Develop Biol 8.CrossRefGoogle ScholarPubMed
Heading, C (2001) Siramesine H Lundbeck. Curr Opin Invest Drugs (London, England: 2000) 2, 266–270.Google ScholarPubMed
Xia, W, Gerard, CM, Liu, L et al. (2005) Combining lapatinib (GW572016), a small molecule inhibitor of ErbB1 and ErbB2 tyrosine kinases, with therapeutic anti-ErbB2 antibodies enhances apoptosis of ErbB2-overexpressing breast cancer cells. Oncogene 24, 6213–6221.CrossRefGoogle Scholar
Ma, S, Henson, E, Chen, Y et al. (2016) Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis 7, e2307–e2307.CrossRefGoogle ScholarPubMed
Zhang, D-L, Ghosh, MC, Rouault, TA (2014) The physiological functions of iron regulatory proteins in iron homeostasis – an update. Front Pharmacol 5, 124.CrossRefGoogle ScholarPubMed
Volz, K (2008) The functional duality of iron regulatory protein 1. Curr Opin Struct Biol 18, 106–111.CrossRefGoogle ScholarPubMed
Franke, KW (1934) A new toxicant occurring naturally in certain samples of plant foodstuffs. 1. Results obtained in preliminary feeding trials. J Nutr 8, 597–608.CrossRefGoogle Scholar
Hatfield, DL, Tsuji, PA, Carlson, BA et al. (2014) Selenium and selenocysteine: roles in cancer, health, and development. Trends Biochem Sci 39, 112–120.CrossRefGoogle Scholar
Conrad, M, Proneth, B (2020) Selenium: tracing another essential element of ferroptotic cell death. Cell Chem Biol 27, 409–419.CrossRefGoogle ScholarPubMed
Bosl, MR, Takaku, K, Oshima, M et al. (1997) Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene (Trsp). Proc Natl Acad Sci U S A 94, 5531–5534.CrossRefGoogle Scholar
Gladyshev, VN, Arner, ES, Berry, MJ et al. (2016) Selenoprotein Gene Nomenclature. J Biol Chem 291, 24036–24040.CrossRefGoogle ScholarPubMed
Kryukov, GV, Castellano, S, Novoselov, SV et al. (2003) Characterization of mammalian selenoproteomes. Science (80-) 300, 1439–1443.CrossRefGoogle ScholarPubMed
Ingold, I, Berndt, C, Schmitt, S et al. (2018) Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell 172, 409–422.e421.CrossRefGoogle ScholarPubMed
Vendeland, SC, Butler, JA, Whanger, PD (1992) Intestinal absorption of selenite, selenate, and selenomethionine in the rat. J Nutr Biochem 3, 359–365.CrossRefGoogle Scholar
Wolffram, S, Ardüser, F, Scharrer, E (1985) In vivo intestinal absorption of selenate and selenite by rats. J Nutr 115, 454–459.CrossRefGoogle ScholarPubMed
Burk, RF, Hill, KE (2009) Selenoprotein P-expression, functions, and roles in mammals. Biochim Biophys Acta 1790, 1441–1447.CrossRefGoogle ScholarPubMed
Chiu-Ugalde, J, Theilig, F, Behrends, T et al. (2010) Mutation of megalin leads to urinary loss of selenoprotein P and selenium deficiency in serum, liver, kidneys and brain. Biochem J 431, 103–111.CrossRefGoogle ScholarPubMed
Alim, I, Caulfield, JT, Chen, Y et al. (2019) Selenium drives a transcriptional adaptive program to block ferroptosis and treat stroke. Cell 177, 1262–1279 e1225.CrossRefGoogle ScholarPubMed
Schomburg, L, Schweizer, U (2009) Hierarchical regulation of selenoprotein expression and sex-specific effects of selenium. Biochim Biophys Acta 1790, 1453–1462.CrossRefGoogle ScholarPubMed
Rayman, MP (2012) Selenium and human health. Lancet 379, 1256–1268.CrossRefGoogle ScholarPubMed
McCarthy, S, Somayajulu, M, Sikorska, M et al. (2004) Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10. Toxicol Appl Pharmacol 201, 21–31.CrossRefGoogle ScholarPubMed
Flint Beal, M, Shults, CW (2003) Effects of Coenzyme Q10 in Huntington’s disease and early Parkinson’s disease. BioFactors 18, 153–161.CrossRefGoogle Scholar
Xie, T, Wang, C, Jin, Y et al. (2020) CoenzymeQ10-induced activation of AMPK-YAP-OPA1 pathway alleviates atherosclerosis by improving mitochondrial function, inhibiting oxidative stress and promoting energy metabolism. Front Pharmacol 11, 1034.CrossRefGoogle ScholarPubMed
Chen, K, Chen, X, Xue, H et al. (2019) Coenzyme Q10 attenuates high-fat diet-induced non-alcoholic fatty liver disease through activation of the AMPK pathway. Food Function 10, 814–823.CrossRefGoogle ScholarPubMed
Lee, SK, Lee, JO, Kim, JH et al. (2012) Coenzyme Q10 increases the fatty acid oxidation through AMPK-mediated PPARα induction in 3T3-L1 preadipocytes. Cell Signal 24, 2329–2336.CrossRefGoogle ScholarPubMed
Mohr, D, Bowry, VW, Stocker, R (1992) Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta Lipids Lipid Metab 1126, 247–254.CrossRefGoogle Scholar
Choy, KJ, Deng, Y-M, Hou, JY et al. (2003) Coenzyme Q10 supplementation inhibits aortic lipid oxidation but fails to attenuate intimal thickening in balloon-injured New Zealand White rabbits. Free Radic Biol Med 35, 300–309.CrossRefGoogle ScholarPubMed
Ahmadvand, H, Mabuchi, H, Nohara, A et al. (2013) Effects of coenzyme Q10 on LDL oxidation in vitro. Acta Med Iran, 12–18.Google ScholarPubMed
Shimada, K, Skouta, R, Kaplan, A et al. (2016) Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat Chem Biol 12, 497–503.CrossRefGoogle ScholarPubMed
Evans, HM, Bishop, KS (1922) On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science (80-) 56, 650–651.CrossRefGoogle ScholarPubMed
Burton, G, Ingold, KU (1986) Vitamin E: application of the principles of physical organic chemistry to the exploration of its structure and function. Acc Chem Res 19, 194–201.CrossRefGoogle Scholar
Khanna, S, Roy, S, Ryu, H et al. (2003) Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegeneration. J Biol Chem 278, 43508–43515.CrossRefGoogle ScholarPubMed
Kagan, VE, Mao, G, Qu, F et al. (2017) Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. 13, 81–90.CrossRefGoogle Scholar
Hambright, WS, Fonseca, RS, Chen, L et al. (2017) Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol 12, 8–17.CrossRefGoogle ScholarPubMed
Wortmann, M, Schneider, M, Pircher, J et al. (2013) Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. Circ Res 113, 408–417.CrossRefGoogle ScholarPubMed
Matsushita, M, Freigang, S, Schneider, C et al. (2015) T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med 212, 555–568.CrossRefGoogle ScholarPubMed
Carlson, BA, Tobe, R, Yefremova, E et al. (2016) Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. Redox Biol 9, 22–31.CrossRefGoogle ScholarPubMed
Seiler, A, Schneider, M, Forster, H et al. (2008) Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-Mediated cell death. Cell Metab 8, 237–248.CrossRefGoogle ScholarPubMed
Hinman, A, Holst, CR, Latham, JC et al. (2018) Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLoS One 13.CrossRefGoogle ScholarPubMed
Valgimigli, L, Pratt, DA (2015) Maximizing the reactivity of phenolic and aminic radical-trapping antioxidants: just add nitrogen! Acc Chem Res 48, 966–975.CrossRefGoogle ScholarPubMed
Nam, TG, Rector, CL, Kim, HY et al. (2007) Tetrahydro-1,8-naphthyridinol analogues of alpha-tocopherol as antioxidants in lipid membranes and low-density lipoproteins. J Am Chem Soc 129, 10211–10219.CrossRefGoogle ScholarPubMed
Zilka, O, Shah, R, Li, B et al. (2017) On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent Sci 3, 232–243.CrossRefGoogle ScholarPubMed
Doll, S, Proneth, B, Tyurina, YY et al. (2017) ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition.Nat Chem Biol 13, 91–98.CrossRefGoogle ScholarPubMed
Lee, J-Y, Nam, M, Son, HY et al. (2020) Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer. Proc Natl Acad Sci 117, 32433–32442.CrossRefGoogle ScholarPubMed
Tang, Y, Zhou, J, Hooi, SC et al. (2018) Fatty acid activation in carcinogenesis and cancer development: Essential roles of long-chain acyl-CoA synthetases. Oncol Lett 16, 1390–1396.Google ScholarPubMed
Doll, S, Proneth, B, Tyurina, YY et al. (2017) ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat Chem Biol 13, 91–98.CrossRefGoogle ScholarPubMed
Das, UN (2019) Saturated fatty acids, MUFAs and PUFAs regulate ferroptosis. Cell Chem Biol 26, 309–311.CrossRefGoogle ScholarPubMed
Mayr, L, Grabherr, F, Schwärzler, J et al. (2020) Dietary lipids fuel GPX4-restricted enteritis resembling Crohn’s disease. Nat Commun 11, 1–15.CrossRefGoogle ScholarPubMed
Perez, MA, Magtanong, L, Dixon, SJ et al. (2020) Dietary lipids induce ferroptosis in Caenorhabditiselegans and human cancer cells. Dev Cell 54, 447–454. e444.CrossRefGoogle ScholarPubMed
Magtanong, L, Ko, PJ, To, M et al. (2019) Exogenous monounsaturated fatty acids promote a ferroptosis-resistant cell state. Cell Chem Biol 26, 420–432 e429.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Garbarino, J, Sturley, SL (2009) Saturated with fat: new perspectives on lipotoxicity. Curr Opin Clin Nutr Metab Care 12, 110–116.CrossRefGoogle ScholarPubMed
Shi, X, Tarazona, P, Brock, TJ et al. (2016) A Caenorhabditis elegans model for ether lipid biosynthesis and function. J Lipid Res 57, 265–275.CrossRefGoogle ScholarPubMed
Wallner, S, Schmitz, G (2011) Plasmalogens the neglected regulatory and scavenging lipid species. Chem Phys Lipids 164, 573–589.CrossRefGoogle ScholarPubMed
Wanders, RJ, Waterham, HR (2006) Peroxisomal disorders: the single peroxisomal enzyme deficiencies. Biochim Biophys Acta Mol Cell Res 1763, 1707–1720.CrossRefGoogle ScholarPubMed
Jewell, JL, Russell, RC, Guan, K-L (2013) Amino acid signalling upstream of mTOR. Nat Rev Mol Cell Biol 14, 133–139.CrossRefGoogle ScholarPubMed
Zoncu, R, Efeyan, A, Sabatini, DM (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12, 21–35.CrossRefGoogle ScholarPubMed
Gomes, AP, Blenis, J (2015) A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways. Curr Opin Biotechnol 34, 110–117.CrossRefGoogle ScholarPubMed
Liu, GY, Sabatini, DM (2020) mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol, 1–21.Google ScholarPubMed
Meng, D, Yang, Q, Wang, H et al. (2020) Glutamine and asparagine activate mTORC1 independently of Rag GTPases. J Biol Chem 295, 2890–2899.CrossRefGoogle ScholarPubMed
Jewell, JL, Kim, YC, Russell, RC et al. (2015) Differential regulation of mTORC1 by leucine and glutamine. Science 347, 194–198.CrossRefGoogle ScholarPubMed
Menon, S, Dibble, CC, Talbott, G et al. (2014) Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell 156, 771–785.CrossRefGoogle ScholarPubMed
Sancak, Y, Bar-Peled, L, Zoncu, R et al. (2010) Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290–303.Google Scholar
Yang, H, Jiang, X, Li, B et al. (2017) Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature 552, 368–373.CrossRefGoogle ScholarPubMed
Carsillo, T, Astrinidis, A, Henske, EP (2000) Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci 97, 6085–6090.CrossRefGoogle ScholarPubMed
Inoki, K, Guan, K-L (2009) Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment. Hum Mol Genet 18, R94–R100.CrossRefGoogle ScholarPubMed
Kwiatkowski, DJ, Manning, BD (2005) Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 14, R251–R258.CrossRefGoogle ScholarPubMed
Yi, J, Zhu, J, Wu, J et al. (2020) Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis. Proc Natl Acad Sci 117, 31189–31197.CrossRefGoogle ScholarPubMed
Han, D, Jiang, L, Gu, X et al. (2020) SIRT3 deficiency is resistant to autophagy-dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels. J Cell Physiol 235, 8839–8851.CrossRefGoogle ScholarPubMed
Zhang, L, Liu, W, Liu, F et al. (2020) IMCA induces ferroptosis mediated by SLC7A11 through the AMPK/mTOR pathway in colorectal cancer. Oxid Med Cell Longev 2020.CrossRefGoogle ScholarPubMed
Guan, P, Wang, N (2014) Mammalian target of rapamycin coordinates iron metabolism with iron-sulfur cluster assembly enzyme and tristetraprolin. Nutrition 30, 968–974.CrossRefGoogle ScholarPubMed
La, P, Yang, G, Dennery, PA (2013) Mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation stabilizes ISCU protein: implications for iron metabolism. J Biol Chem 288, 12901–12909.CrossRefGoogle ScholarPubMed
Bayeva, M, Khechaduri, A, Puig, S et al. (2012) mTOR regulates cellular iron homeostasis through tristetraprolin. Cell Metab 16, 645–657.CrossRefGoogle ScholarPubMed
Przybylowski, P, Malyszko, J, Macdougall, I et al. (2013) Iron metabolism, hepcidin, and anemia in orthotopic heart transplantation recipients treated with mammalian target of rapamycin. Transplant Proc 45, 387–390.CrossRefGoogle ScholarPubMed
Baba, Y, Higa, JK, Shimada, BK et al. (2018) Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol 314, H659–H668.CrossRefGoogle ScholarPubMed
Hardie, DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8, 774–785.CrossRefGoogle ScholarPubMed
Atkinson, DE, Fall, L (1967) Adenosine triphosphate conservation in biosynthetic regulation: Escherichia coli phosphoribosylpyrophosphate synthase. J Biol Chem 242, 3241–3242.CrossRefGoogle ScholarPubMed
Atkinson, DE, Walton, GM (1967) Adenosine triphosphate conservation in metabolic regulation: rat liver citrate cleavage enzyme. J Biol Chem 242, 3239–3241.CrossRefGoogle ScholarPubMed
Xiao, B, Sanders, MJ, Underwood, E et al. (2011) Structure of mammalian AMPK and its regulation by ADP. Nature 472, 230–233.CrossRefGoogle ScholarPubMed
Hardie, DG, Hawley, SA, Scott, JW (2006) AMP-activated protein kinase – development of the energy sensor concept. J Physiol 574, 7–15.CrossRefGoogle ScholarPubMed
Hawley, SA, Boudeau, J, Reid, JL et al. (2003) Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2, 1–16.CrossRefGoogle Scholar
Lee, H, Zandkarimi, F, Zhang, Y (2020) Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol 22, 225–234.CrossRefGoogle ScholarPubMed
Li, C, Dong, X, Du, W et al. (2020) LKB1-AMPK axis negatively regulates ferroptosis by inhibiting fatty acid synthesis. Signal Transduct Target Ther 5, 1–4.CrossRefGoogle ScholarPubMed
Currais, A, Huang, L, Goldberg, J et al. (2019) Elevating acetyl-CoA levels reduces aspects of brain aging. eLife 8, e47866.CrossRefGoogle ScholarPubMed
Hay, N (2016) Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? Nat Rev Cancer 16, 635.CrossRefGoogle ScholarPubMed
Song, X, Zhu, S, Chen, P et al. (2018) AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc − activity. Curr Biol 28, 2388–2399.e2385.CrossRefGoogle ScholarPubMed
Liang, XH, Jackson, S, Seaman, M et al. (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676.CrossRefGoogle ScholarPubMed
Zhong, Y, Tian, F, Ma, H et al. (2020) FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells. Life Sci 260, 118077.CrossRefGoogle ScholarPubMed
Zhao, Y, Li, M, Yao, X et al. (2020) HCAR1/MCT1 regulates tumor ferroptosis through the lactate-mediated AMPK-SCD1 activity and its therapeutic implications. Cell Rep 33, 108487.CrossRefGoogle ScholarPubMed
Xu, J, Ji, J, Yan, X-H (2012) Cross-talk between AMPK and mTOR in regulating energy balance. Crit Rev Food Sci Nutr 52, 373–381.CrossRefGoogle ScholarPubMed
Gao, M, Yi, J, Zhu, J et al. (2019) Role of mitochondria in ferroptosis. Mol Cell 73, 354–363.e353.CrossRefGoogle ScholarPubMed
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–e2716.CrossRefGoogle ScholarPubMed
Zhang, W, Gai, C, Ding, D et al. (2018) Targeted p53 on small-molecules-induced ferroptosis in cancers. Front Oncol 8, 507.CrossRefGoogle ScholarPubMed
Venkatesh, S, Li, M, Saito, T et al. (2019) Mitochondrial LonP1 protects cardiomyocytes from ischemia/reperfusion injury in vivo. J Mol Cell Cardiol 128, 38–50.CrossRefGoogle ScholarPubMed
Fang, X, Wang, H (2019) Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci U S A 116, 2672–2680.CrossRefGoogle ScholarPubMed
Gaweł, S, Wardas, M, Niedworok, E et al. (2004) Malondialdehyde (MDA) as a lipid peroxidation marker. Wiadomosci lekarskie (Warsaw, Poland: 1960) 57, 453–455.Google Scholar
Gonzalez-Rivas, PA, Chauhan, SS, Ha, M et al. (2020) Effects of heat stress on animal physiology, metabolism, and meat quality: a review. Meat Sci 162, 108025.CrossRefGoogle ScholarPubMed
Ross, FA, MacKintosh, C, Hardie, DG (2016) AMP-activated protein kinase: a cellular energy sensor that comes in 12 flavours. FEBS J 283, 2987–3001.CrossRefGoogle ScholarPubMed
Hardie, DG (2015) Molecular pathways: is AMPK a friend or a foe in cancer? Clin Cancer Res 21, 3836–3840.CrossRefGoogle ScholarPubMed
Kohjima, M, Higuchi, N, Kato, M et al. (2008) SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med 21, 507–511.Google Scholar
Li, W, Wong, CC, Zhang, X et al. (2018) CAB39L elicited an anti-Warburg effect via a LKB1-AMPK-PGC1α axis to inhibit gastric tumorigenesis. Oncogene 37, 6383–6398.CrossRefGoogle Scholar
Maher, P (2018) Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: implications for age-related neurodegenerative diseases. Free Radic Biol Med 115, 92–104.CrossRefGoogle ScholarPubMed
Chen, P-H, Wu, J, Xu, Y et al. (2021) Zinc transporter ZIP7 is a novel determinant of ferroptosis. Cell Death Dis 12, 1–12.Google ScholarPubMed
Chen, X, Comish, PB, Tang, D et al. (2021) Characteristics and biomarkers of ferroptosis. Front Cell Develop Biol 9, 30.Google ScholarPubMed
Pintus, F, Floris, G, Rufini, A (2012) Nutrient availability links mitochondria, apoptosis, and obesity. Aging (Albany NY) 4, 734.CrossRefGoogle Scholar
Molina, AJ, Wikstrom, JD, Stiles, L et al. (2009) Mitochondrial networking protects β-cells from nutrient-induced apoptosis. Diabetes 58, 2303–2315.CrossRefGoogle ScholarPubMed
Lee, JM, Wagner, M, Xiao, R et al. (2014) Nutrient-sensing nuclear receptors coordinate autophagy. Nature 516, 112–115.CrossRefGoogle ScholarPubMed
Russell, RC, Yuan, H-X, Guan, K-L (2014) Autophagy regulation by nutrient signaling. Cell Res 24, 42–57.CrossRefGoogle ScholarPubMed