KEGG PATHWAY: ko04216

PATHWAY: ko04216

Entry

ko04216                     Pathway

Name

Ferroptosis

Description

Ferroptosis is a regulated form of cell death and characterized by a production of reactive oxygen species (ROS) from accumulated iron and lipid peroxidation. It can be induced by experimental compounds (e.g.,erastin, RSL3) or clinical drugs(e.g., sulfasalazine, sorafenib) in cancer cell and certain normal cells. It is involved in multiple physiological and pathological processes, such as cancer cell death, neurodegenerative disease, tissue damage and acute renal failure.

Class

Cellular Processes; Cell growth and death

Pathway map

ko04216

Ferroptosis

Other DBs

GO:

0097707

Orthology

K06519

solute carrier family 3, member 2

K13869

solute carrier family 7 (L-type amino acid transporter), member 11

K04451

tumor protein p53

K11204

glutamate--cysteine ligase catalytic subunit [EC:6.3.2.2]

K11205

glutamate--cysteine ligase regulatory subunit

K21456

glutathione synthase [EC:6.3.2.3]

K05361

phospholipid-hydroperoxide glutathione peroxidase [EC:1.11.1.12]

K01897

long-chain-fatty-acid---CoA ligase [EC:6.2.1.3]

K13515

lysophospholipid acyltransferase 5 [EC:2.3.1.23 2.3.1.-]

K00460

arachidonate 15-lipoxygenase [EC:1.13.11.33]

K00657

diamine N-acetyltransferase [EC:2.3.1.57]

K14736

transferrin

K06503

transferrin receptor

K10142

metalloreductase STEAP3 [EC:1.16.1.-]

K21398

natural resistance-associated macrophage protein 2

K14714

solute carrier family 39 (zinc transporter), member 8

K14720

solute carrier family 39 (zinc transporter), member 14

K13162

poly(rC)-binding protein 2

K14685

solute carrier family 40 (iron-regulated transporter), member 1

K13624

ceruloplasmin [EC:1.16.3.1]

K12889

poly(rC)-binding protein 1

K00522

ferritin heavy chain [EC:1.16.3.1]

K13625

ferritin light chain

K10435

microtubule-associated protein 1 light chain

K08339

autophagy-related protein 5

K08337

ubiquitin-like modifier-activating enzyme ATG7

K09289

nuclear receptor coactivator 4

K05634

prion protein

K00510

heme oxygenase 1 [EC:1.14.14.18]

K15040

voltage-dependent anion channel protein 2

K15041

voltage-dependent anion channel protein 3

K21421

NADPH oxidase 2 [EC:1.-.-.-]

K18495

ferritin, mitochondrial [EC:1.16.3.1]

Compound

C00010

CoA

C00024

Acetyl-CoA

C00025

L-Glutamate

C00027

Hydrogen peroxide

C00032

Heme

C00051

Glutathione

C00097

L-Cysteine

C00127

Glutathione disulfide

C00129

Isopentenyl diphosphate

C00219

Arachidonate

C00356

(S)-3-Hydroxy-3-methylglutaryl-CoA

C00418

(R)-Mevalonate

C00491

L-Cystine

C00669

gamma-L-Glutamyl-L-cysteine

C02249

Arachidonyl-CoA

C02477

alpha-Tocopherol

C11378

Ubiquinone-10

C14818

Fe2+

C14819

Fe3+

C16170

(7Z,10Z,13Z,16Z)-Docosatetraenoyl-CoA

C16527

Adrenic acid

C16844

Hydroxyl radical

C21478

Erastin

C21479

RSL3

C21480

1-Octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine

C21481

1-Octadecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-sn-glycero-3-phosphoethanolamine

C21482

1-Octadecanoyl-2-(15S-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine

C21483

1-Octadecanoyl-2-(15S-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine

C21484

1-Octadecanoyl-sn-glycero-3-phosphoethanolamine

D00448

Sulfasalazine (USP/INN)

D08524

Sorafenib (USAN/INN)

Reference

PMID:26775689

Authors

Conrad M, Angeli JP, Vandenabeele P, Stockwell BR

Title

Regulated necrosis: disease relevance and therapeutic opportunities.

Journal

Nat Rev Drug Discov 15:348-66 (2016)
DOI:10.1038/nrd.2015.6

Reference

PMID:26653790

Authors

Yang WS, Stockwell BR

Title

Ferroptosis: Death by Lipid Peroxidation.

Journal

Trends Cell Biol 26:165-76 (2016)
DOI:10.1016/j.tcb.2015.10.014

Reference

PMID:27842066

Authors

Kagan VE, Mao G, Qu F, Angeli JP, Doll S, Croix CS, Dar HH, Liu B, Tyurin VA, Ritov VB, Kapralov AA, Amoscato AA, Jiang J, Anthonymuthu T, Mohammadyani D, Yang Q, Proneth B, Klein-Seetharaman J, Watkins S, Bahar I, Greenberger J, Mallampalli RK, Stockwell BR, Tyurina YY, Conrad M, Bayir H

Title

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis.

Journal

Nat Chem Biol 13:81-90 (2017)
DOI:10.1038/nchembio.2238

Reference

PMID:27842067

Authors

D'Herde K, Krysko DV

Title

Ferroptosis: Oxidized PEs trigger death.

Journal

Nat Chem Biol 13:4-5 (2017)
DOI:10.1038/nchembio.2261

Reference

PMID:28082232

Authors

Guiney SJ, Adlard PA, Bush AI, Finkelstein DI, Ayton S

Title

Ferroptosis and cell death mechanisms in Parkinson's disease.

Journal

Neurochem Int 104:34-48 (2017)
DOI:10.1016/j.neuint.2017.01.004

Reference

PMID:26725301

Authors

Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y

Title

Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease.

Journal

Trends Biochem Sci 41:274-86 (2016)
DOI:10.1016/j.tibs.2015.11.012

Reference

PMID:26794443

Authors

Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, Kang R, Tang D

Title

Ferroptosis: process and function.

Journal

Cell Death Differ 23:369-79 (2016)
DOI:10.1038/cdd.2015.158

Reference

PMID:27791175

Authors

Murphy ME

Title

Ironing out how p53 regulates ferroptosis.

Journal

Proc Natl Acad Sci U S A 113:12350-12352 (2016)
DOI:10.1073/pnas.1615159113

Reference

PMID:28129536

Authors

Muckenthaler MU, Rivella S, Hentze MW, Galy B

Title

A Red Carpet for Iron Metabolism.

Journal

Cell 168:344-361 (2017)
DOI:10.1016/j.cell.2016.12.034

Reference

PMID:27860262

Authors

Yu H, Guo P, Xie X, Wang Y, Chen G

Title

Ferroptosis, a new form of cell death, and its relationships with tumourous diseases.

Journal

J Cell Mol Med 21:648-657 (2017)
DOI:10.1111/jcmm.13008

Reference

PMID:27314071

Authors

Wang SJ, Ou Y, Jiang L, Gu W

Title

Ferroptosis: A missing puzzle piece in the p53 blueprint?

Journal

Mol Cell Oncol 3:e1046581 (2016)
DOI:10.1080/23723556.2015.1046581

Reference

PMID:27048822

Authors

Cao JY, Dixon SJ

Title

Mechanisms of ferroptosis.

Journal

Cell Mol Life Sci 73:2195-209 (2016)
DOI:10.1007/s00018-016-2194-1

Reference

PMID:26436293

Authors

Mancias JD, Pontano Vaites L, Nissim S, Biancur DE, Kim AJ, Wang X, Liu Y, Goessling W, Kimmelman AC, Harper JW

Title

Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis.

Journal

Elife 4:e10308 (2015)
DOI:10.7554/eLife.10308

Reference

PMID:28066232

Authors

Wang YQ, Chang SY, Wu Q, Gou YJ, Jia L, Cui YM, Yu P, Shi ZH, Wu WS, Gao G, Chang YZ

Title

The Protective Role of Mitochondrial Ferritin on Erastin-Induced Ferroptosis.

Journal

Front Aging Neurosci 8:308 (2016)
DOI:10.3389/fnagi.2016.00308

Reference

PMID:26405158

Authors

Kwon MY, Park E, Lee SJ, Chung SW

Title

Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death.

Journal

Oncotarget 6:24393-403 (2015)
DOI:10.18632/oncotarget.5162

Reference

PMID:22632964

Authors

Reed JC, Pellecchia M

Title

Ironing out cell death mechanisms.

Journal

Cell 149:963-5 (2012)
DOI:10.1016/j.cell.2012.05.009

Related
pathway

ko00480

Glutathione metabolism

ko00900

Terpenoid backbone biosynthesis

LinkDB

DBGET integrated database retrieval system