Diverse biological functions of vitamin K: from coagulation to ferroptosis.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
received:
16
01
2023
accepted:
12
05
2023
medline:
27
6
2023
pubmed:
20
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
Vitamin K is essential for several physiological processes, such as blood coagulation, in which it serves as a cofactor for the conversion of peptide-bound glutamate to γ-carboxyglutamate in vitamin K-dependent proteins. This process is driven by the vitamin K cycle facilitated by γ-carboxyglutamyl carboxylase, vitamin K epoxide reductase and ferroptosis suppressor protein-1, the latter of which was recently identified as the long-sought-after warfarin-resistant vitamin K reductase. In addition, vitamin K has carboxylation-independent functions. Akin to ubiquinone, vitamin K acts as an electron carrier for ATP production in some organisms and prevents ferroptosis, a type of cell death hallmarked by lipid peroxidation. In this Perspective, we provide an overview of the diverse functions of vitamin K in physiology and metabolism and, at the same time, offer a perspective on its role in ferroptosis together with ferroptosis suppressor protein-1. A comparison between vitamin K and ubiquinone, from an evolutionary perspective, may offer further insights into the manifold roles of vitamin K in biology.
Identifiants
pubmed: 37337123
doi: 10.1038/s42255-023-00821-y
pii: 10.1038/s42255-023-00821-y
doi:
Substances chimiques
Vitamin K
12001-79-5
Ubiquinone
1339-63-5
Vitamin K Epoxide Reductases
EC 1.17.4.4
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
924-932Informations de copyright
© 2023. Springer Nature Limited.
Références
Mladenka, P. et al. Vitamin K—sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity. Nutr. Rev. 80, 677–698 (2022).
pubmed: 34472618
doi: 10.1093/nutrit/nuab061
Tabb, M. M. et al. Vitamin K
pubmed: 12920130
doi: 10.1074/jbc.M303136200
Nowicka, B. & Kruk, J. Occurrence, biosynthesis and function of isoprenoid quinones. Biochim. Biophys. Acta 1797, 1587–1605 (2010).
pubmed: 20599680
doi: 10.1016/j.bbabio.2010.06.007
Mishima, E. et al. A non-canonical vitamin K cycle is a potent ferroptosis suppressor. Nature 608, 778–783 (2022).
pubmed: 35922516
pmcid: 9402432
doi: 10.1038/s41586-022-05022-3
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
Mishima, E. & Conrad, M. Nutritional and metabolic control of ferroptosis. Annu. Rev. Nutr. 42, 275–309 (2022).
pubmed: 35650671
doi: 10.1146/annurev-nutr-062320-114541
Dam, H. The antihaemorrhagic vitamin of the chick. Biochem. J. 29, 1273–1285 (1935).
pubmed: 16745789
pmcid: 1266625
doi: 10.1042/bj0291273
Dam, H. et al. Isolierung des vitamins K in hochgereinigter form. Helv. Chim. Acta 22, 310–313 (1939).
doi: 10.1002/hlca.19390220141
McKee, R. W., Binkley, S. B., MacCorquodale, D. W., Thayer, S. A. & Doisy, E. A. The isolation of vitamins K
doi: 10.1021/ja01874a507
Lehmann, J. Vitamin K as a prophylactic in 13,000 infants. Lancet 243, 493–494 (1944).
doi: 10.1016/S0140-6736(00)74175-4
Esmon, C. T., Sadowski, J. A. & Suttie, J. W. A new carboxylation reaction. The vitamin K-dependent incorporation of H-14-CO
pubmed: 1141226
doi: 10.1016/S0021-9258(19)41365-3
Stenflo, J., Fernlund, P., Egan, W. & Roepstorff, P. Vitamin K-dependent modifications of glutamic acid residues in prothrombin. Proc. Natl Acad. Sci. USA 71, 2730–2733 (1974).
pubmed: 4528109
pmcid: 388542
doi: 10.1073/pnas.71.7.2730
Stenflo, J. A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization. J. Biol. Chem. 251, 355–363 (1976).
pubmed: 1245477
doi: 10.1016/S0021-9258(17)33886-3
Stenflo, J. & Jonsson, M. Protein S, a new vitamin K-dependent protein from bovine plasma. FEBS Lett. 101, 377–381 (1979).
pubmed: 109318
doi: 10.1016/0014-5793(79)81048-0
Villa, J. K. D., Diaz, M. A. N., Pizziolo, V. R. & Martino, H. S. D. Effect of vitamin K in bone metabolism and vascular calcification: a review of mechanisms of action and evidences. Crit. Rev. Food Sci. Nutr. 57, 3959–3970 (2017).
pubmed: 27437760
doi: 10.1080/10408398.2016.1211616
Bouckaert, J. H. & Said, A. H. Fracture healing by vitamin K. Nature 185, 849 (1960).
pubmed: 13803194
doi: 10.1038/185849a0
Walker, C. S. et al. On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Evidence for a gamma-glutamyl carboxylase in Drosophila. J. Biol. Chem. 276, 7769–7774 (2001).
pubmed: 11110799
doi: 10.1074/jbc.M009576200
Brown, M. A. et al. Precursors of novel Gla-containing conotoxins contain a carboxy-terminal recognition site that directs gamma-carboxylation. Biochemistry 44, 9150–9159 (2005).
pubmed: 15966739
doi: 10.1021/bi0503293
Li, T., Yang, C. T., Jin, D. & Stafford, D. W. Identification of a Drosophila vitamin K-dependent gamma-glutamyl carboxylase. J. Biol. Chem. 275, 18291–18296 (2000).
pubmed: 10748045
doi: 10.1074/jbc.M001790200
Schofield, F. W. A brief account of a disease in cattle simulating hemorrhagic septicaemia due to feeding sweet clover. Can. Vet. J. 3, 3274–3278 (1922).
Campbell, H. A. & Link, K. P. Studies on the hemorrhagic sweet clover disease: iv. The isolation and crystallization of the hemorrhagic agent. J. Biol. Chem. 138, 21–33 (1941).
doi: 10.1016/S0021-9258(18)51407-1
Overman, R. S. et al. Studies on the hemorrhagic sweet clover disease: xiii. Anticoagulant activity and structure in the 4-hydroxycoumarin group. J. Biol. Chem. 153, 5–24 (1944).
doi: 10.1016/S0021-9258(18)51207-2
Holmes, R. W. & Love, J. Suicide attempt with warfarin, a bishydroxycoumarin-like rodenticide. JAMA 148, 935–937 (1952).
doi: 10.1001/jama.1952.62930110003013a
Whitlon, D. S., Sadowski, J. A. & Suttie, J. W. Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry 17, 1371–1377 (1978).
pubmed: 646989
doi: 10.1021/bi00601a003
Berkner, K. L. Vitamin K-dependent carboxylation. Vitam. Horm. 78, 131–156 (2008).
pubmed: 18374193
doi: 10.1016/S0083-6729(07)00007-6
Bell, R. G. & Matschiner, J. T. Warfarin and the inhibition of vitamin K activity by an oxide metabolite. Nature 237, 32–33 (1972).
pubmed: 4555434
doi: 10.1038/237032a0
Sherman, P. A. & Sander, E. G. Vitamin K epoxide reductase: evidence that vitamin K dihydroquinone is a product of vitamin K epoxide reduction. Biochem. Biophys. Res. Commun. 103, 997–1005 (1981).
pubmed: 7332587
doi: 10.1016/0006-291X(81)90908-6
Tie, J. K. & Stafford, D. W. Structural and functional insights into enzymes of the vitamin K cycle. J. Thromb. Haemost. 14, 236–247 (2016).
pubmed: 26663892
pmcid: 5073812
doi: 10.1111/jth.13217
Wu, S. M., Cheung, W. F., Frazier, D. & Stafford, D. W. Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science 254, 1634–1636 (1991).
pubmed: 1749935
doi: 10.1126/science.1749935
Li, T. et al. Identification of the gene for vitamin K epoxide reductase. Nature 427, 541–544 (2004).
pubmed: 14765195
doi: 10.1038/nature02254
Rost, S. et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427, 537–541 (2004).
pubmed: 14765194
doi: 10.1038/nature02214
Wallin, R. & Hutson, S. Vitamin K-dependent carboxylation. Evidence that at least two microsomal dehydrogenases reduce vitamin K
pubmed: 6799508
doi: 10.1016/S0021-9258(19)68073-7
Shearer, M. J. & Okano, T. Key pathways and regulators of vitamin K function and intermediary metabolism. Annu. Rev. Nutr. 38, 127–151 (2018).
pubmed: 29856932
doi: 10.1146/annurev-nutr-082117-051741
Chu, P. H., Huang, T. Y., Williams, J. & Stafford, D. W. Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2. Proc. Natl Acad. Sci. USA 103, 19308–19313 (2006).
pubmed: 17164330
pmcid: 1698442
doi: 10.1073/pnas.0609401103
Wallin, R., Patrick, S. D. & Ballard, J. O. Vitamin K antagonism of coumarin intoxication in the rat. Thromb. Haemost. 55, 235–239 (1986).
pubmed: 2424118
doi: 10.1055/s-0038-1661528
Lowenthal, J. & Macfarlane, J. A. The nature of the antagonism between vitamin K and indirect anticoagulants. J. Pharmacol. Exp. Ther. 143, 273–277 (1964).
pubmed: 14161135
Ingram, B. O., Turbyfill, J. L., Bledsoe, P. J., Jaiswal, A. K. & Stafford, D. W. Assessment of the contribution of NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) to the reduction of vitamin K in wild-type and NQO1-deficient mice. Biochem. J. 456, 47–54 (2013).
pubmed: 24015818
doi: 10.1042/BJ20130639
Ross, D. et al. NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem. Biol. Interact. 129, 77–97 (2000).
pubmed: 11154736
doi: 10.1016/S0009-2797(00)00199-X
Doll, S. et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693–698 (2019).
pubmed: 31634899
doi: 10.1038/s41586-019-1707-0
Bersuker, K. et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688–692 (2019).
pubmed: 31634900
pmcid: 6883167
doi: 10.1038/s41586-019-1705-2
Kaye, J. B. et al. Warfarin pharmacogenomics in diverse populations. Pharmacotherapy 37, 1150–1163 (2017).
pubmed: 28672100
pmcid: 6913521
doi: 10.1002/phar.1982
Nutescu, E., Chuatrisorn, I. & Hellenbart, E. Drug and dietary interactions of warfarin and novel oral anticoagulants: an update. J. Thromb. Thrombolysis 31, 326–343 (2011).
pubmed: 21359645
doi: 10.1007/s11239-011-0561-1
Jin, D. Y. et al. A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. Nat. Commun. 14, 828 (2023).
pubmed: 36788244
pmcid: 9929328
doi: 10.1038/s41467-023-36446-8
Napolitano, M., Mariani, G. & Lapecorella, M. Hereditary combined deficiency of the vitamin K-dependent clotting factors. Orphanet J. Rare Dis. 5, 21 (2010).
pubmed: 20630065
pmcid: 2913942
doi: 10.1186/1750-1172-5-21
Brenner, B. et al. A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors. Blood 92, 4554–4559 (1998).
pubmed: 9845520
doi: 10.1182/blood.V92.12.4554
De Vilder, E. Y., Debacker, J. & Vanakker, O. M. GGCX-associated phenotypes: an overview in search of genotype–phenotype correlations. Int. J. Mol. Sci. https://doi.org/10.3390/ijms18020240 (2017).
Oldenburg, J. et al. Congenital deficiency of vitamin K-dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex. Thromb. Haemost. 84, 937–941 (2000).
pubmed: 11154138
doi: 10.1055/s-0037-1614152
Pauli, R. M., Lian, J. B., Mosher, D. F. & Suttie, J. W. Association of congenital deficiency of multiple vitamin K-dependent coagulation factors and the phenotype of the warfarin embryopathy: clues to the mechanism of teratogenicity of coumarin derivatives. Am. J. Hum. Genet. 41, 566–583 (1987).
pubmed: 3499071
pmcid: 1684308
Azuma, K. et al. Liver-specific gamma-glutamyl carboxylase-deficient mice display bleeding diathesis and short life span. PLoS ONE 9, e88643 (2014).
pubmed: 24520408
pmcid: 3919827
doi: 10.1371/journal.pone.0088643
Zhu, A. et al. Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase. Blood 109, 5270–5275 (2007).
pubmed: 17327402
pmcid: 1890832
doi: 10.1182/blood-2006-12-064188
Shiba, S. et al. Vitamin K-dependent gamma-glutamyl carboxylase in sertoli cells is essential for male fertility in mice. Mol. Cell Biol. https://doi.org/10.1128/MCB.00404-20 (2021).
Azuma, K. et al. Osteoblast-specific gamma-glutamyl carboxylase-deficient mice display enhanced bone formation with aberrant mineralization. J. Bone Miner. Res. 30, 1245–1254 (2015).
pubmed: 25600070
doi: 10.1002/jbmr.2463
Spohn, G. et al. VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. Thromb. Haemost. 101, 1044–1050 (2009).
pubmed: 19492146
doi: 10.1160/TH09-03-0204
LeBlanc, J. G. et al. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol. 24, 160–168 (2013).
pubmed: 22940212
doi: 10.1016/j.copbio.2012.08.005
Shearer, M. J., McBurney, A. & Barkhan, P. Studies on the absorption and metabolism of phylloquinone (vitamin K
pubmed: 4617407
doi: 10.1016/S0083-6729(08)60025-4
Narushima, K., Takada, T., Yamanashi, Y. & Suzuki, H. Niemann-pick C1-like 1 mediates alpha-tocopherol transport. Mol. Pharmacol. 74, 42–49 (2008).
pubmed: 18403720
doi: 10.1124/mol.107.043034
Takada, T. et al. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy. Sci. Transl. Med. 7, 275ra223 (2015).
doi: 10.1126/scitranslmed.3010329
Goncalves, A. et al. Intestinal scavenger receptors are involved in vitamin K
pubmed: 25228690
pmcid: 4215251
doi: 10.1074/jbc.M114.587659
Hirota, Y. et al. Menadione (vitamin K
pubmed: 24085302
pmcid: 3829156
doi: 10.1074/jbc.M113.477356
Nakagawa, K. et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature 468, 117–121 (2010).
pubmed: 20953171
doi: 10.1038/nature09464
Okano, T. et al. Conversion of phylloquinone (vitamin K
pubmed: 18083713
doi: 10.1074/jbc.M702971200
Thijssen, H. H. & Drittij-Reijnders, M. J. Vitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone-4. Br. J. Nutr. 75, 121–127 (1996).
pubmed: 8785182
doi: 10.1079/BJN19960115
Shearer, M. J. Vitamin K in parenteral nutrition. Gastroenterology 137, S105–S118 (2009).
pubmed: 19874942
doi: 10.1053/j.gastro.2009.08.046
Araki, S. & Shirahata, A. Vitamin K deficiency bleeding in infancy. Nutrients https://doi.org/10.3390/nu12030780 (2020).
Zipursky, A. Prevention of vitamin K deficiency bleeding in newborns. Br. J. Haematol. 104, 430–437 (1999).
pubmed: 10086774
doi: 10.1046/j.1365-2141.1999.01104.x
Shea, M. K. et al. Vitamin K status and cognitive function in adults with chronic kidney disease: the chronic renal insufficiency cohort. Curr. Dev. Nutr. 6, nzac111 (2022).
pubmed: 35957738
pmcid: 9362761
doi: 10.1093/cdn/nzac111
Berkner, K. L. & Runge, K. W. Vitamin K-dependent protein activation: normal gamma-glutamyl carboxylation and disruption in disease. Int. J. Mol. Sci. https://doi.org/10.3390/ijms23105759 (2022).
Hayes, D. M. Neonatal anemia due to water-soluble vitamin K analogue: case report. N. C. Med. J. 22, 270–271 (1961).
pubmed: 13712478
Ansbacher, S., Corwin, W. C. & Thomas, B. G. H. Toxicity of menadione, menadiol and esters. J. Pharmacol. Exp. Ther. 75, 111 (1942).
Loor, G. et al. Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis. Free Radic. Biol. Med. 49, 1925–1936 (2010).
pubmed: 20937380
pmcid: 3005834
doi: 10.1016/j.freeradbiomed.2010.09.021
Goto, S. et al. Prodrugs for skin delivery of menahydroquinone-4 an active form of vitamin K
pubmed: 31137618
pmcid: 6566782
doi: 10.3390/ijms20102548
Ichikawa, T., Horie-Inoue, K., Ikeda, K., Blumberg, B. & Inoue, S. Vitamin K
pubmed: 17909264
doi: 10.1677/JME-07-0048
Ohsaki, Y. et al. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor kappaB through the repression of IKKalpha/beta phosphorylation. J. Nutr. Biochem. 21, 1120–1126 (2010).
pubmed: 20149620
doi: 10.1016/j.jnutbio.2009.09.011
Hirota, Y. & Suhara, Y. New aspects of vitamin K research with synthetic ligands: transcriptional activity via SXR and neural differentiation activity. Int. J. Mol. Sci. https://doi.org/10.3390/ijms20123006 (2019).
Jiang, X., Stockwell, B. R. & Conrad, M. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell Biol. 22, 266–282 (2021).
pubmed: 33495651
pmcid: 8142022
doi: 10.1038/s41580-020-00324-8
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
Vervoort, L. M., Ronden, J. E. & Thijssen, H. H. The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation. Biochem. Pharmacol. 54, 871–876 (1997).
pubmed: 9354587
doi: 10.1016/S0006-2952(97)00254-2
Li, J. et al. Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. J. Neurosci. 23, 5816–5826 (2003).
pubmed: 12843286
pmcid: 6741273
doi: 10.1523/JNEUROSCI.23-13-05816.2003
Kolbrink, B. et al. Vitamin K
pubmed: 35763128
pmcid: 9239973
doi: 10.1007/s00018-022-04416-w
Viswanathan, V. S. et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547, 453–457 (2017).
pubmed: 28678785
pmcid: 5667900
doi: 10.1038/nature23007
Misima, E. et al. DHODH inhibitors sensitize cancer cells to ferroptosis via FSP1 inhibition. Res. Sq. https://doi.org/10.21203/rs.3.rs-2190326/v1 (2022).
doi: 10.21203/rs.3.rs-2190326/v1
Hiratsuka, T. et al. An alternative menaquinone biosynthetic pathway operating in microorganisms. Science 321, 1670–1673 (2008).
pubmed: 18801996
doi: 10.1126/science.1160446
Meganathan, R. & Kwon, O. Biosynthesis of menaquinone (vitamin K
Brettel, K. & Leibl, W. Electron transfer in photosystem I. Biochim. Biophys. Acta 1507, 100–114 (2001).
pubmed: 11687210
doi: 10.1016/S0005-2728(01)00202-X
Wang, L. et al. The phytol phosphorylation pathway is essential for the biosynthesis of phylloquinone, which is required for photosystem I stability in Arabidopsis. Mol. Plant 10, 183–196 (2017).
pubmed: 28007557
doi: 10.1016/j.molp.2016.12.006
Vos, M. et al. Vitamin K
pubmed: 22582012
doi: 10.1126/science.1218632
Cerqua, C. et al. Vitamin K
pubmed: 31024065
pmcid: 6484000
doi: 10.1038/s41598-019-43014-y
Hirota, Y. et al. Functional characterization of the vitamin K
pubmed: 25874989
pmcid: 4398444
doi: 10.1371/journal.pone.0125737
Nashimoto, S., Takekawa, Y., Takekuma, Y., Sugawara, M. & Sato, Y. Transport via Niemann–Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone. Drug Metab. Pharmacokinet. 35, 527–533 (2020).
pubmed: 33036883
doi: 10.1016/j.dmpk.2020.08.002
Ilbert, M. & Bonnefoy, V. Insight into the evolution of the iron oxidation pathways. Biochim. Biophys. Acta 1827, 161–175 (2013).
pubmed: 23044392
doi: 10.1016/j.bbabio.2012.10.001
Bergdoll, L., Ten Brink, F., Nitschke, W., Picot, D. & Baymann, F. From low- to high-potential bioenergetic chains: thermodynamic constraints of Q-cycle function. Biochim. Biophys. Acta 1857, 1569–1579 (2016).
pubmed: 27328272
doi: 10.1016/j.bbabio.2016.06.006
Distefano, A. M. et al. Heat stress induces ferroptosis-like cell death in plants. J. Cell Biol. 216, 463–476 (2017).
pubmed: 28100685
pmcid: 5294777
doi: 10.1083/jcb.201605110
Aguilera, A. et al. C-ferroptosis is an iron-dependent form of regulated cell death in cyanobacteria. J. Cell Biol. https://doi.org/10.1083/jcb.201911005 (2022).
Bogacz, M. & Krauth-Siegel, R. L. Tryparedoxin peroxidase deficiency commits trypanosomes to ferroptosis-type cell death. Elife https://doi.org/10.7554/eLife.37503 (2018).
Shen, Q., Liang, M., Yang, F., Deng, Y. Z. & Naqvi, N. I. Ferroptosis contributes to developmental cell death in rice blast. New Phytol. 227, 1831–1846 (2020).
pubmed: 32367535
doi: 10.1111/nph.16636
Perez, M. A., Magtanong, L., Dixon, S. J. & Watts, J. L. Dietary lipids induce ferroptosis in Caenorhabditis elegans and human cancer cells. Dev. Cell 54, 447–454 (2020).
pubmed: 32652074
pmcid: 7483868
doi: 10.1016/j.devcel.2020.06.019
Conrad, M. et al. Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev. 32, 602–619 (2018).
pubmed: 29802123
pmcid: 6004068
doi: 10.1101/gad.314674.118
Vats, K. et al. Keratinocyte death by ferroptosis initiates skin inflammation after UVB exposure. Redox Biol. 47, 102143 (2021).
pubmed: 34592565
pmcid: 8487085
doi: 10.1016/j.redox.2021.102143
Singhal, R. & Shah, Y. M. Oxygen battle in the gut: hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine. J. Biol. Chem. 295, 10493–10505 (2020).
pubmed: 32503843
pmcid: 7383395
doi: 10.1074/jbc.REV120.011188