Ferroptosis is a type of programmed cell death which is distinct from apoptosis and necrosis, since cell death occurs due to failure of the glutathione-dependent antioxidant defenses in regulating iron. Reactive oxygen species (ROS) are produced from accumulated iron and lipid peroxidation (regulated by GrX4 and 15-LO). Ferroptosis is important in several physiological and pathological processes, including cancer cell death, mitochondrial dysfunction induced epilepsy and neurodegenerative disease. Ferroptosis can be induced to treat multiple forms of cancer by inhibiting tumor growth, although the exact mechanism is unknown. Ferroptosis has also been linked to neurodegenerative disease, possibly through increased inflammation caused by release of lipid metabolites. Description adapted from [https://www.genome.jp/dbget-bin/www_bget?pathway+hsa04216 KEGG] and [https://en.wikipedia.org/wiki/Ferroptosis Wikipedia]. ff4 e31 ac8 Glutathione e31 adf e31 adf eb6 ac8 e31 ac8 aka LOOH e31 ac8 b4a aka 15-lipoxygenase (EC 1.13.11.33); ALOX15 c35 adf db8 a48 eb6 adf a48 adf bc5 bc5 aka vatiquinone (α-tocotrienol quinone) e98 adf aka Poly Unsaturated Fatty Acid c35 e31 adf bc6 f1e e31 e31 e31 e31 aka LOOH e31 aka Poly Unsaturated Fatty Acid aka Poly Unsaturated Fatty Acid c35 bc5 bc6 ac8 c35 e31 e98 e31 e31 e31 c35 e31 e98 c35 e31 c35 adf ac8 adf ferroptosis pathway PW:0002626 Pathway Ontology mitochondrial disease pathway PW:0001669 Pathway Ontology epilepsy DOID:1826 Human Disease Ontology cell death pathway PW:0000275 Pathway Ontology unsaturated fatty acid biosynthetic pathway PW:0001137 Pathway Ontology hsa04216 KEGG Pathway Ferroptosis - Homo sapiens (human) https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa04216 30042655 PubMed Targeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration. Front Neurosci 2018 Abdalkader M Lampinen R Kanninen KM Malm TM Liddell JR 33268902 PubMed Ferroptosis: molecular mechanisms and health implications. Cell Res 2021 Tang D Chen X Kang R Kroemer G 33043019 PubMed Oxidative Damage and Antioxidant Defense in Ferroptosis. Front Cell Dev Biol 2020 Kuang F Liu J Tang D Kang R 32760721 PubMed Ferroptosis in Acute Central Nervous System Injuries: The Future Direction? Front Cell Dev Biol 2020 Shen L Lin D Li X Wu H Lenahan C Pan Y Xu W Chen Y Shao A Zhang J 30925886 PubMed Ferroptosis, a new form of cell death: opportunities and challenges in cancer. J Hematol Oncol 2019 Mou Y Wang J Wu J He D Zhang C Duan C Li B 33495651 PubMed Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol 2021 Jiang X Stockwell BR Conrad M 30110365 PubMed Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLoS One 2018 Hinman A Holst CR Latham JC Bruegger JJ Ulas G McCusker KP Amagata A Davis D Hoff KG Kahn-Kirby AH Kim V Kosaka Y Lee E Malone SA Mei JJ Richards SJ Rivera V Miller G Trimmer JK Shrader WD 31101865 PubMed Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer 2019 Friedmann Angeli JP Krysko DV Conrad M 32256352 PubMed Ferroptosis and Its Potential Role in Human Diseases. Front Pharmacol 2020 Han C Liu Y Dai R Ismail N Su W Li B 32015325 PubMed Ferroptosis: past, present and future. Cell Death Dis 2020 Li J Cao F Yin HL Huang ZJ Lin ZT Mao N Sun B Wang G 30921410 PubMed Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy. PLoS One 2019 Kahn-Kirby AH Amagata A Maeder CI Mei JJ Sideris S Kosaka Y Hinman A Malone SA Bruegger JJ Wang L Kim V Shrader WD Hoff KG Latham JC Ashley EA Wheeler MT Bertini E Carrozzo R Martinelli D Dionisi-Vici C Chapman KA Enns GM Gahl W Wolfe L Saneto RP Johnson SC Trimmer JK Klein MB Holst CR 31740582 PubMed Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1. J Biol Chem 2020 Nishizawa H Matsumoto M Shindo T Saigusa D Kato H Suzuki K Sato M Ishii Y Shimokawa H Igarashi K