Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10521)
Regulator Name Transcription factor A, mitochondrial (TFAM)
Synonyms
Mitochondrial transcription factor 1; Transcription factor 6; Transcription factor 6-like 2
    Click to Show/Hide
Gene Name TFAM
Gene ID 7019
Regulator Type Protein coding
Uniprot ID Q00059
Sequence
MAFLRSMWGVLSALGRSGAELCTGCGSRLRSPFSFVYLPRWFSSVLASCPKKPVSSYLRF
SKEQLPIFKAQNPDAKTTELIRRIAQRWRELPDSKKKIYQDAYRAEWQVYKEEISRFKEQ
LTPSQIMSLEKEIMDKHLKRKAMTKKKELTLLGKPKRPRSAYNVYVAERFQEAKGDSPQE
KLKTVKENWKNLSDSEKELYIQHAKEDETRYHNEMKSWEEQMIEVGRKDLLRRTIKKQRK
YGAEEC

    Click to Show/Hide
Function
Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation . Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites. Is able to unwind DNA. Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes. Required for maintenance of normal levels of mitochondrial DNA . May play a role in organizing and compacting mitochondrial DNA.

    Click to Show/Hide
HGNC ID
HGNC:11741
KEGG ID hsa:7019
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TFAM 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
Browse Drug
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Responsed Drug ZZW-115 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis.

    Click to Show/Hide
Response regulation The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Responsed Drug ZZW-115 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis.

    Click to Show/Hide
Response regulation The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115.
Pancreatic cancer [ICD-11: 2C10]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcription factor A, mitochondrial (TFAM) Protein coding
 Regulator Info 
Responsed Drug ZZW-115 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis.

    Click to Show/Hide
Response regulation The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcription factor A, mitochondrial (TFAM) Protein coding
 Regulator Info 
Responsed Drug ZZW-115 Investigative
 Drug Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis.

    Click to Show/Hide
Response regulation The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115.
ZZW-115 [Investigative]
 Drug Info 
In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Pancreatic cancer ICD-11: 2C10
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis.

    Click to Show/Hide
Response regulation The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115.
Experiment 2 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 MIA PaCa-2 cells Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0428
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
Xenografts with MiaPaCa-2 and HepG2 cells in nude mice and treated them for 4 or 3 weeks, respectively, with vehicle alone and 2.5 or 5.0 mg/kg/day of ZZW-115. Then, we measured the GPX4 activity and analyzed the mRNA levels of the key genes involved in ferroptosis by qRT-PCR analysis.

    Click to Show/Hide
Response regulation The expression of TFAM, a key regulator of mitochondrial biogenesis, is downregulated by ZZW-115. Forced expression of TFAM is able to rescue morphological and functional mitochondrial alterations, ROS production, and cell death induced by ZZW-115 or genetic inhibition of NUPR1. These results have been validated in xenografts induced with pancreatic ductal adenocarcinoma (PDAC)- and hepatocellular carcinoma (HCC)-derived cells in nude mice during the treatment with ZZW-115.
References
Ref 1 NUPR1 inhibitor ZZW-115 induces ferroptosis in a mitochondria-dependent manner. Cell Death Discov. 2021 Oct 1;7(1):269. doi: 10.1038/s41420-021-00662-2.