Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10360)
Regulator Name E3 ubiquitin-protein ligase MARCHF5 (MARCHF5)
Synonyms
MARCH5, RNF153; Membrane-associated RING finger protein 5; Membrane-associated RING-CH protein V; Mitochondrial ubiquitin ligase; RING finger protein 153; RING-type E3 ubiquitin transferase MARCHF5
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Gene Name MARCHF5
Gene ID 54708
Regulator Type Protein coding
Uniprot ID Q9NX47
Sequence
MPDQALQQMLDRSCWVCFATDEDDRTAEWVRPCRCRGSTKWVHQACLQRWVDEKQRGNST
ARVACPQCNAEYLIVFPKLGPVVYVLDLADRLISKACPFAAAGIMVGSIYWTAVTYGAVT
VMQVVGHKEGLDVMERADPLFLLIGLPTIPVMLILGKMIRWEDYVLRLWRKYSNKLQILN
SIFPGIGCPVPRIPAEANPLADHVSATRILCGALVFPTIATIVGKLMFSSVNSNLQRTIL
GGIAFVAIKGAFKVYFKQQQYLRQAHRKILNYPEQEEA

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Function
Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1.

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HGNC ID
HGNC:26025
KEGG ID hsa:54708
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
MARCHF5 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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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 Cardiomyopathy ICD-11: BC43
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
In Vivo Model
In all experiments using KO mice (male, 8-12 weeks), we used age-matched, tamoxifen-treated MerCreMer single-genotype animals as controls. For inducing cardiac-specific knockout of MITOL, an ethanol-corn oil emulsion of tamoxifen (TAX; H5648, Sigma-Aldrich) was injected intraperitoneally per day of 30 mg tamoxifen/kg body weight (150 mg/kg total) for 5 days.

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Response regulation MITOL/ MARCH5 is an E3 ubiquitin ligase that plays a crucial role in the control of mitochondrial quality and function. The mitochondrial ubiquitin ligase MITOL is identified as a novel regulator of DOX-induced cardiomyopathy. A knockdown of MITOL in cardiomyocytes reduced GPX4 to induce the accumulation of lipid peroxide, resulting in ferroptosis.
Cardiomyopathy [ICD-11: BC43]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator E3 ubiquitin-protein ligase MARCHF5 (MARCHF5) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hCMs (Human cardiomyocytes)
In Vivo Model
In all experiments using KO mice (male, 8-12 weeks), we used age-matched, tamoxifen-treated MerCreMer single-genotype animals as controls. For inducing cardiac-specific knockout of MITOL, an ethanol-corn oil emulsion of tamoxifen (TAX; H5648, Sigma-Aldrich) was injected intraperitoneally per day of 30 mg tamoxifen/kg body weight (150 mg/kg total) for 5 days.

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Response regulation MITOL/ MARCH5 is an E3 ubiquitin ligase that plays a crucial role in the control of mitochondrial quality and function. The mitochondrial ubiquitin ligase MITOL is identified as a novel regulator of DOX-induced cardiomyopathy. A knockdown of MITOL in cardiomyocytes reduced GPX4 to induce the accumulation of lipid peroxide, resulting in ferroptosis.
References
Ref 1 MITOL/MARCH5 determines the susceptibility of cardiomyocytes to doxorubicin-induced ferroptosis by regulating GSH homeostasis. J Mol Cell Cardiol. 2021 Dec;161:116-129. doi: 10.1016/j.yjmcc.2021.08.006. Epub 2021 Aug 12.