Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10083)
Regulator Name Dihydrolipoyl dehydrogenase, mitochondrial (DLD)
Synonyms
GCSL, LAD, PHE3; Dihydrolipoamide dehydrogenase; Glycine cleavage system L protein
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Gene Name DLD
Gene ID 1738
Regulator Type Protein coding
Uniprot ID P09622
Sequence
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKA
AQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNL
DKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNIL
IATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVT
AVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGK
AEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGP
MLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK
FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDI
ARVCHAHPTLSEAFREANLAASFGKSINF

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Family Class-I pyridine nucleotide-disulfide oxidoreductase family
Function
Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched- chain amino acid-dehydrogenase complex). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion. A fraction of the 2- oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A. In monomeric form may have additional moonlighting function as serine protease. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.

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HGNC ID
HGNC:2898
KEGG ID hsa:1738
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
DLD 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).
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Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Citrate cycle hsa00020
Cell Process Cell ferroptosis
In Vitro Model
 NH-3 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8126
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
NH-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8132
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN9 cells with shDLD or vector control were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route).

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Response regulation Dihydrolipoamide dehydrogenase (DLD) regulates cystine deprivation-induced ferroptosis in head and neck cancer. DLD inhibition decreases both lipid peroxidation and ferrous iron accumulation, resulting in ferroptosis suppression.
Head neck squamous cell carcinoma [ICD-11: 2D60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Dihydrolipoyl dehydrogenase, mitochondrial (DLD) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Citrate cycle hsa00020
Cell Process Cell ferroptosis
In Vitro Model
 NH-3 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8126
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
NH-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_8132
In Vivo Model
Six-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN9 cells with shDLD or vector control were subcutaneously injected into the bilateral flank of nude mice. From the day when gross nodules were detected in tumor implants, mice were subjected to different treatments: vehicle or sulfasalazine (250 mg/kg daily per intraperitoneal route).

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Response regulation Dihydrolipoamide dehydrogenase (DLD) regulates cystine deprivation-induced ferroptosis in head and neck cancer. DLD inhibition decreases both lipid peroxidation and ferrous iron accumulation, resulting in ferroptosis suppression.
References
Ref 1 Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer. Redox Biol. 2020 Feb;30:101418. doi: 10.1016/j.redox.2019.101418. Epub 2020 Jan 7.