Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10255)
Regulator Name Glutaredoxin-related protein 5, mitochondrial (GLRX5)
Synonyms
C14orf87; Monothiol glutaredoxin-5
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Gene Name GLRX5
Gene ID 51218
Regulator Type Protein coding
Uniprot ID Q86SX6
Sequence
MSGSLGRAAAALLRWGRGAGGGGLWGPGVRAAGSGAGGGGSAEQLDALVKKDKVVVFLKG
TPEQPQCGFSNAVVQILRLHGVRDYAAYNVLDDPELRQGIKDYSNWPTIPQVYLNGEFVG
GCDILLQMHQNGDLVEELKKLGIHSALLDEKKDQDSK

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Family Glutaredoxin family
Function
Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer. Receives 2Fe/2S clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion. Required for normal regulation of hemoglobin synthesis by the iron- sulfur protein ACO1.

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HGNC ID
HGNC:20134
KEGG ID hsa:51218
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
GLRX5 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
Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor/Driver
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

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Response regulation The suppression of GLRX5 activated the IRE-binding activity of IRP and canonical iron-starvation responsive proteins (increased TfR, decreased FTH), resulting in increased intracellular free iron. The data suggest that inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis.
Solute carrier family 40 member 1 (SLC40A1) [Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

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Response regulation Inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. Increased IRP and TfR and decreased Fpn and FTH boosted up intracellular free iron, resulting in lipid peroxidation and ferroptosis in vitro and in vivo.
Ferritin heavy chain (FTH1) [Suppressor; Marker]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

    Click to Show/Hide
Response regulation Inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. Increased IRP and TfR and decreased Fpn and FTH boosted up intracellular free iron, resulting in lipid peroxidation and ferroptosis in vitro and in vivo.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

    Click to Show/Hide
Response regulation The suppression of GLRX5 activated the IRE-binding activity of IRP and canonical iron-starvation responsive proteins (increased TfR, decreased FTH), resulting in increased intracellular free iron. The data suggest that inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis.
Head neck squamous cell carcinoma [ICD-11: 2D60]
 Disease Info 
In total 4 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutaredoxin-related protein 5, mitochondrial (GLRX5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

    Click to Show/Hide
Response regulation The suppression of GLRX5 activated the IRE-binding activity of IRP and canonical iron-starvation responsive proteins (increased TfR, decreased FTH), resulting in increased intracellular free iron. The data suggest that inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutaredoxin-related protein 5, mitochondrial (GLRX5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

    Click to Show/Hide
Response regulation Inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. Increased IRP and TfR and decreased Fpn and FTH boosted up intracellular free iron, resulting in lipid peroxidation and ferroptosis in vitro and in vivo.
Experiment 3 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutaredoxin-related protein 5, mitochondrial (GLRX5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

    Click to Show/Hide
Response regulation Inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis. Increased IRP and TfR and decreased Fpn and FTH boosted up intracellular free iron, resulting in lipid peroxidation and ferroptosis in vitro and in vivo.
Experiment 4 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Glutaredoxin-related protein 5, mitochondrial (GLRX5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 AMC-HN-3 cells Laryngeal squamous cell carcinoma Homo sapiens CVCL_5961
HN3R (Human head and neck squamous cell carcinoma cell)
HN4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_IS30
HN4R (Human head and neck squamous cell carcinoma cell)
In Vivo Model
Five-week-old athymic BALB/c male nude mice (nu/nu) were purchased from Central Lab Animal Inc. (Seoul, Republic of Korea). HN4R cells with vector control or shGLRX5 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 SAS (250 mg/kg daily per intraperitoneal route). Each group included seven mice.

    Click to Show/Hide
Response regulation The suppression of GLRX5 activated the IRE-binding activity of IRP and canonical iron-starvation responsive proteins (increased TfR, decreased FTH), resulting in increased intracellular free iron. The data suggest that inhibition of GLRX5 predisposes therapy-resistant head and neck cancer (HNC) cells to ferroptosis.
References
Ref 1 Inhibition of Glutaredoxin 5 predisposes Cisplatin-resistant Head and Neck Cancer Cells to Ferroptosis. Theranostics. 2020 Jun 19;10(17):7775-7786. doi: 10.7150/thno.46903. eCollection 2020.