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].ff4e31ac8Glutathionee31adfe31adfeb6ac8e31ac8aka LOOHe31ac8b4aaka 15-lipoxygenase (EC 1.13.11.33); ALOX15c35adfdb8a48eb6adfa48adfbc5bc5aka vatiquinone (α-tocotrienol quinone)e98adfaka Poly Unsaturated Fatty Acidc35e31adfbc6f1ee31e31e31e31aka LOOHe31aka Poly Unsaturated Fatty Acidaka Poly Unsaturated Fatty Acidc35bc5bc6ac8c35e31e98e31e31e31c35e31e98c35e31c35adfac8adfferroptosis pathwayPW:0002626Pathway Ontologymitochondrial disease pathwayPW:0001669Pathway OntologyepilepsyDOID:1826Human Disease Ontologycell death pathwayPW:0000275Pathway Ontologyunsaturated fatty acid biosynthetic pathwayPW:0001137Pathway Ontologyhsa04216KEGG PathwayFerroptosis - Homo sapiens (human)https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa0421630042655PubMedTargeting Nrf2 to Suppress Ferroptosis and Mitochondrial Dysfunction in Neurodegeneration.Front Neurosci2018Abdalkader MLampinen RKanninen KMMalm TMLiddell JR33268902PubMedFerroptosis: molecular mechanisms and health implications.Cell Res2021Tang DChen XKang RKroemer G33043019PubMedOxidative Damage and Antioxidant Defense in Ferroptosis.Front Cell Dev Biol2020Kuang FLiu JTang DKang R32760721PubMedFerroptosis in Acute Central Nervous System Injuries: The Future Direction?Front Cell Dev Biol2020Shen LLin DLi XWu HLenahan CPan YXu WChen YShao AZhang J30925886PubMedFerroptosis, a new form of cell death: opportunities and challenges in cancer.J Hematol Oncol2019Mou YWang JWu JHe DZhang CDuan CLi B33495651PubMedFerroptosis: mechanisms, biology and role in disease.Nat Rev Mol Cell Biol2021Jiang XStockwell BRConrad M30110365PubMedVitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase.PLoS One2018Hinman AHolst CRLatham JCBruegger JJUlas GMcCusker KPAmagata ADavis DHoff KGKahn-Kirby AHKim VKosaka YLee EMalone SAMei JJRichards SJRivera VMiller GTrimmer JKShrader WD31101865PubMedFerroptosis at the crossroads of cancer-acquired drug resistance and immune evasion.Nat Rev Cancer2019Friedmann Angeli JPKrysko DVConrad M32256352PubMedFerroptosis and Its Potential Role in Human Diseases.Front Pharmacol2020Han CLiu YDai RIsmail NSu WLi B32015325PubMedFerroptosis: past, present and future.Cell Death Dis2020Li JCao FYin HLHuang ZJLin ZTMao NSun BWang G30921410PubMedTargeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy.PLoS One2019Kahn-Kirby AHAmagata AMaeder CIMei JJSideris SKosaka YHinman AMalone SABruegger JJWang LKim VShrader WDHoff KGLatham JCAshley EAWheeler MTBertini ECarrozzo RMartinelli DDionisi-Vici CChapman KAEnns GMGahl WWolfe LSaneto RPJohnson SCTrimmer JKKlein MBHolst CR31740582PubMedFerroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1.J Biol Chem2020Nishizawa HMatsumoto MShindo TSaigusa DKato HSuzuki KSato MIshii YShimokawa HIgarashi K