Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10165)
Regulator Name Isocitrate dehydrogenase [NADP], mitochondrial (IDH2)
Synonyms
ICD-M; IDP; NADP(+)-specific ICDH; Oxalosuccinate decarboxylase
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Gene Name IDH2
Gene ID 3418
Regulator Type Protein coding
Uniprot ID P48735
Sequence
MAGYLRVVRSLCRASGSRPAWAPAALTAPTSQEQPRRHYADKRIKVAKPVVEMDGDEMTR
IIWQFIKEKLILPHVDIQLKYFDLGLPNRDQTDDQVTIDSALATQKYSVAVKCATITPDE
ARVEEFKLKKMWKSPNGTIRNILGGTVFREPIICKNIPRLVPGWTKPITIGRHAHGDQYK
ATDFVADRAGTFKMVFTPKDGSGVKEWEVYNFPAGGVGMGMYNTDESISGFAHSCFQYAI
QKKWPLYMSTKNTILKAYDGRFKDIFQEIFDKHYKTDFDKNKIWYEHRLIDDMVAQVLKS
SGGFVWACKNYDGDVQSDILAQGFGSLGLMTSVLVCPDGKTIEAEAAHGTVTRHYREHQK
GRPTSTNPIASIFAWTRGLEHRGKLDGNQDLIRFAQMLEKVCVETVESGAMTKDLAGCIH
GLSNVKLNEHFLNTTDFLDTIKSNLDRALGRQ

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Family Isocitrate and isopropylmalate dehydrogenases family
Function
Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex.

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HGNC ID
HGNC:5383
KEGG ID hsa:3418
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
IDH2 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Fibrosarcoma ICD-11: 2B53
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Hepa 1-6 cells Hepatocellular carcinoma Mus musculus CVCL_0327
In Vivo Model
Eight week-old male nude mice weighing approximately 21-23 g were divided into two groups (DMSO group and erastin group) with 5 mice per group. Each mouse was injected with 5 x 106 cells transfected non-targeting shRNA and idh2-targeting shRNA on the left and right hind legs, respectively. Erastin was administered intraperitoneally at 5 mg/kg for 15 consecutive days starting on the same day as tumor injection.

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Response regulation IDH2 is major enzyme that produces NADPH, which is essential for GSH turnover. The data suggest that decreased growth of tumors with IDH2-knockdown is due to inhibition of Gpx4 followed by a shortage of GSH, resulting in ferroptotic cell death in Fibrosarcoma.
Fibrosarcoma [ICD-11: 2B53]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Isocitrate dehydrogenase [NADP], mitochondrial (IDH2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Hepa 1-6 cells Hepatocellular carcinoma Mus musculus CVCL_0327
In Vivo Model
Eight week-old male nude mice weighing approximately 21-23 g were divided into two groups (DMSO group and erastin group) with 5 mice per group. Each mouse was injected with 5 x 106 cells transfected non-targeting shRNA and idh2-targeting shRNA on the left and right hind legs, respectively. Erastin was administered intraperitoneally at 5 mg/kg for 15 consecutive days starting on the same day as tumor injection.

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Response regulation IDH2 is major enzyme that produces NADPH, which is essential for GSH turnover. The data suggest that decreased growth of tumors with IDH2-knockdown is due to inhibition of Gpx4 followed by a shortage of GSH, resulting in ferroptotic cell death in Fibrosarcoma.
References
Ref 1 Down-regulation of IDH2 sensitizes cancer cells to erastin-induced ferroptosis. Biochem Biophys Res Commun. 2020 Apr 30;525(2):366-371. doi: 10.1016/j.bbrc.2020.02.093. Epub 2020 Feb 21.