Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10061)
Target Name Voltage-dependent anion-selective channel protein 2 (VDAC2)
Synonyms
Outer mitochondrial membrane protein porin 2
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Gene Name VDAC2
Sequence
MATHGQTCARPMCIPPSYADLGKAARDIFNKGFGFGLVKLDVKTKSCSGVEFSTSGSSNT
DTGKVTGTLETKYKWCEYGLTFTEKWNTDNTLGTEIAIEDQICQGLKLTFDTTFSPNTGK
KSGKIKSSYKRECINLGCDVDFDFAGPAIHGSAVFGYEGWLAGYQMTFDSAKSKLTRNNF
AVGYRTGDFQLHTNVNDGTEFGGSIYQKVCEDLDTSVNLAWTSGTNCTRFGIAAKYQLDP
TASISAKVNNSSLIGVGYTQTLRPGVKLTLSALVDGKSINAGGHKVGLALELEA

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Family Eukaryotic mitochondrial porin family
Function
Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol. Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway.

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Gene ID 7417
Uniprot ID
P45880
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
VDAC2 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
E3 ubiquitin-protein ligase NEDD4 (NEDD4)
 Regulator Info 
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Drug Robustaflavone Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Response Description Robustaflavone A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways.
Melanoma [ICD-11: 2C30]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
G-361 cells Melanoma Homo sapiens CVCL_1220
MeWo cells Melanoma Homo sapiens CVCL_0445
SK-MEL-2 cells (MEK inhibitor-resistant) cells Melanoma Homo sapiens CVCL_0069
SK-MEL-3 cells Cutaneous melanoma Homo sapiens CVCL_0550
SK-MEL-24 cells Melanoma Homo sapiens CVCL_0599
WM2032 cells Melanoma Homo sapiens CVCL_0B68
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
NU/NU Nude mice were purchased from Charles River (Beijing). To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the left posterior flanks of 7-week-old immunodeficient female nude mice.

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Response Description Knockdown of Nedd4 leads to elevated protein level of VDAC2/3, which increased the sensitivity of melanoma cells to erastin both in vitro and in vivo.
E3 ubiquitin-protein ligase NEDD4 (NEDD4)
 Regulator Info 
Robustaflavone [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Suppressor
Responsed Disease Breast cancer [ICD-11: 2C60]
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
Response Description Robustaflavone A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways.
References
Ref 1 Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway. Bioorg Chem. 2021 Apr;109:104744. doi: 10.1016/j.bioorg.2021.104744. Epub 2021 Feb 17.
Ref 2 Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. Nat Commun. 2020 Jan 23;11(1):433. doi: 10.1038/s41467-020-14324-x.