General Information of the Ferroptosis Target (ID: TAR10026)
Target Name Glutaminase liver isoform, mitochondrial (GLS2)
Synonyms
L-glutaminase; L-glutamine amidohydrolase
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Gene Name GLS2
Sequence
MRSMKALQKALSRAGSHCGRGGWGHPSRSPLLGGGVRHHLSEAAAQGRETPHSHQPQHQD
HDSSESGMLSRLGDLLFYTIAEGQERIPIHKFTTALKATGLQTSDPRLRDCMSEMHRVVQ
ESSSGGLLDRDLFRKCVSSNIVLLTQAFRKKFVIPDFEEFTGHVDRIFEDVKELTGGKVA
AYIPQLAKSNPDLWGVSLCTVDGQRHSVGHTKIPFCLQSCVKPLTYAISISTLGTDYVHK
FVGKEPSGLRYNKLSLNEEGIPHNPMVNAGAIVVSSLIKMDCNKAEKFDFVLQYLNKMAG
NEYMGFSNATFQSEKETGDRNYAIGYYLKEKKCFPKGVDMMAALDLYFQLCSVEVTCESG
SVMAATLANGGICPITGESVLSAEAVRNTLSLMHSCGMYDFSGQFAFHVGLPAKSAVSGA
ILLVVPNVMGMMCLSPPLDKLGNSHRGTSFCQKLVSLFNFHNYDNLRHCARKLDPRREGA
EIRNKTVVNLLFAAYSGDVSALRRFALSAMDMEQKDYDSRTALHVAAAEGHIEVVKFLIE
ACKVNPFAKDRWGNIPLDDAVQFNHLEVVKLLQDYQDSYTLSETQAEAAAEALSKENLES
MV

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Family Glutaminase family
Function
Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha- ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.

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Gene ID 27165
Uniprot ID
Q9UI32
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
GLS2 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
hsa-miR-190a-5p (miRNA)
Acute myocardial infarction [ICD-11: BA41]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Pathway Response Glutathione metabolism hsa00480
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
HEK-293T cells Normal Homo sapiens CVCL_0063
Response Description MiR-190a-5p negatively regulate ferroptosis via directly targeting GLS2 in rat cardiomyocyte H9c2 cells. Forced expression of miR-190a-5p inhibited GLS2, resulting in downregulation of ROS, MDA and Fe2+accumulation. In summary, miR-190a-5p plays an essential role in regulation of ferroptosis of cardiomyocytes and suggest a potential therapeutic target for myocardial infarction.
Double-stranded RNA-specific adenosine deaminase (ADAR)
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
U251-TR3 cells Astrocytoma Homo sapiens CVCL_1G29
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
Nude mice (four-week-old, female, 3/group) were purchased from Model Animal Research Center of Nanjing University. 2.5 x 105 luciferase labeled pcDNA3.1-ATXN8OS/GLS2 were transfected into U251 cells. After 48 h, transfected cells were injected stereotactically into thebrainof nude mice. In the first week after operation, TMZ was given to treat nude mice by oral gavage (66 mg/kg per day for 5 days), with vehicle as control. Bioluminescence imaging (IVIS Spectrum; PerkinElmer, USA) was applied for confirming the formation of intracranial tumor. 28 days late, all the mice were sacrificed. The resected tumors were measure at Lipid ROS and intracellular iron level. The whole experiments were approved by ethic committee of Shanxi Provincial Peoples Hospital.

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Response Description Rescue experiments indicated that ATXN8OS modulated TMZ-resistance of glioma through GLS2. In conclusion, ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway.
ATXN8OS (IncRNA)
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
U251-TR3 cells Astrocytoma Homo sapiens CVCL_1G29
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
In Vivo Model
Nude mice (four-week-old, female, 3/group) were purchased from Model Animal Research Center of Nanjing University. 2.5 x 105 luciferase labeled pcDNA3.1-ATXN8OS/GLS2 were transfected into U251 cells. After 48 h, transfected cells were injected stereotactically into thebrainof nude mice. In the first week after operation, TMZ was given to treat nude mice by oral gavage (66 mg/kg per day for 5 days), with vehicle as control. Bioluminescence imaging (IVIS Spectrum; PerkinElmer, USA) was applied for confirming the formation of intracranial tumor. 28 days late, all the mice were sacrificed. The resected tumors were measure at Lipid ROS and intracellular iron level. The whole experiments were approved by ethic committee of Shanxi Provincial Peoples Hospital.

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Response Description Rescue experiments indicated that ATXN8OS modulated TMZ-resistance of glioma through GLS2. In conclusion, ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway.
Unspecific Regulator
Neurotoxicity [ICD-11: NE61]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Responsed Drug Formaldehyde Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

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Response Description Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
Unspecific Regulator
Formaldehyde [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Responsed Disease Neurotoxicity [ICD-11: NE61]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Sprague-Dawley (SD, weight: 200-220 g) rats were obtained from Hunan SJA laboratory animal company (Changsha, Hunan, China). SD rats were anaesthetized by sodium pentobarbital (45 mg/kg, i.p.) and secured in a stereotaxic frame. The aseptically cannula was implanted into lateral ventricle according to the following coordinates: AP: -1mm; ML: 2 mm; DV: 4 mm. During experiment, the unilateral ventricle of rats was received 2.5 ul FA (0.1, 1, 10 umol) according to the experiment scheme in vivo.

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Response Description Formaldehyde (FA)-induced neurotoxicity is implicated in neuronal ferroptosis. FA induced cell death in HT22 cells, and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells for the formaldehyde-induced neurotoxicity.
References
Ref 1 miR-190a-5p regulates cardiomyocytes response to ferroptosis via directly targeting GLS2. Biochem Biophys Res Commun. 2021 Aug 20;566:9-15. doi: 10.1016/j.bbrc.2021.05.100. Epub 2021 Jun 7.
Ref 2 Long non-coding RNA ATXN8OS promotes ferroptosis and inhibits the temozolomide-resistance of gliomas through the ADAR/GLS2 pathway. Brain Res Bull. 2022 Aug;186:27-37. doi: 10.1016/j.brainresbull.2022.04.005. Epub 2022 Apr 20.
Ref 3 Formaldehyde induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect. Toxicology. 2021 Jan 30;448:152650. doi: 10.1016/j.tox.2020.152650. Epub 2020 Nov 28.