General Information of the Ferroptosis Regulator (ID: REG10229)
Regulator Name Tafazzin (TAFAZZIN)
Synonyms
Protein G4.5
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Gene Name TAFAZZIN
Gene ID 6901
Regulator Type Protein coding
Uniprot ID Q16635
Sequence
MPLHVKWPFPAVPPLTWTLASSVVMGLVGTYSCFWTKYMNHLTVHNREVLYELIEKRGPA
TPLITVSNHQSCMDDPHLWGILKLRHIWNLKLMRWTPAAADICFTKELHSHFFSLGKCVP
VCRGDGVYQKGMDFILEKLNHGDWVHIFPEGKVNMSSEFLRFKWGIGRLIAECHLNPIIL
PLWHVGMNDVLPNSPPYFPRFGQKITVLIGKPFSALPVLERLRAENKSAVEMRKALTDFI
QEEFQHLKTQAEQLHNHLQPGR

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Family Taffazin family
Function
Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1',3'-bis-[1,2-diacyl-sn-glycero-3-phospho]- glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary for adequate mitochondrial function. Its role in cellular physiology is to improve mitochondrial performance. CL is critical for the coassembly of lipids and proteins in mitochondrial membranes, for instance, remodeling of the acyl groups of CL in the mitochondrial inner membrane affects the assembly and stability of respiratory chain complex IV and its supercomplex forms. Catalyzes the transacylacion between phospholipids and lysophospholipids, with the highest rate being between phosphatidylcholine (1,2-diacyl-sn-glycero- 3-phosphocholine or PC) and CL. Catalyzes both 1-acyl-sn-glycero-3- phosphocholine (lysophosphatidylcholine or LPC) reacylation and PC-CL transacylation, that means, it exchanges acyl groups between CL and PC by a combination of forward and reverse transacylations. Also catalyzes transacylations between other phospholipids such as phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine or PE) and CL, between PC and PE, and between PC and phosphatidate (1,2-diacyl-sn-glycero-3-phosphate or PA), although at lower rate. Not regiospecific, it transfers acyl groups into any of the sn-1 and sn-2 positions of the monolysocardiolipin (MLCL), which is an important prerequisite for uniformity and symmetry in CL acyl distribution. Cannot transacylate dilysocardiolipin (DLCL), thus, the role of MLCL is limited to that of an acyl acceptor. CoA-independent, it can reshuffle molecular species within a single phospholipid class. Redistributes fatty acids between MLCL, CL, and other lipids, which prolongs the half-life of CL. Its action is completely reversible, which allows for cyclic changes, such as fission and fusion or bending and flattening of the membrane. Hence, by contributing to the flexibility of the lipid composition, it plays an important role in the dynamics of mitochondria membranes. Essential for the final stage of spermatogenesis, spermatid individualization. Required for the initiation of mitophagy. Required to ensure progression of spermatocytes through meiosis. Exon 7 of human tafazzin is essential for catalysis.

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HGNC ID
HGNC:11577
KEGG ID hsa:6901
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TAFAZZIN 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
NADPH oxidase 4 (NOX4) [Driver]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Hereditary Leiomyomatosis ICD-11: 2C90
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
RCC4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0498
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
HEK-293T cells Normal Homo sapiens CVCL_0063
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
In Vivo Model
One million 786O cells with or without shTAZ were implanted subcutaneously into the healthy 8-week-old JAX NOD.CB17-PrkdcSCID-J mice; both male and female mice were used. Once tumor volume reached 120 mm3, mice were randomized into control or erastin treatment group. The vehicle (ORA-plus) or erastin (0.1 ml of 4 mg/ml erastin) was administrated by oral gavage twice daily for 20 days.

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Response regulation Cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for renal cell carcinoma (RCC) and other TAZ-activated tumors.
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
HEK-293T cells Normal Homo sapiens CVCL_0063
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HLE cells Hepatocellular carcinoma Homo sapiens CVCL_1281
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
In Vivo Model
SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks.

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Response regulation In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Tafazzin (TAFAZZIN) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
HEK-293T cells Normal Homo sapiens CVCL_0063
SNU-398 cells Adult hepatocellular carcinoma Homo sapiens CVCL_0077
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HLE cells Hepatocellular carcinoma Homo sapiens CVCL_1281
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
In Vivo Model
SNU398-parental cells, SNU398-shLuc, or SNU398-shYAP/TAZ cells (106 in 100 ul PBS) were implanted into the left flanks of immunodeficient NOD/SCID; common receptor-/-(NSG) mice. When tumors were palpable, Sorafenib (LC Laboratories, S-8502) was applied at 20 mg/kg daily via gavage, SSA (Sulfasalazine, Sigma, S0883) was given at 120 mg/kg daily by intraperitoneal injection, 20 mM BSO (Lbuthionine-sulfoximine, Sigma, B2515) was given in the drinking water for 3 weeks.

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Response regulation In a TEAD-dependent manner, YAP/TAZ induce the expression of SLC7A11, a key transporter maintaining intracellular glutathione homeostasis, thus enabling hepatocellular carcinoma cells to overcome Sorafenib-induced ferroptosis. At the same time, YAP/TAZ sustain the protein stability, nuclear localization, and transcriptional activity of ATF4 which in turn cooperates to induce SLC7A11 expression.
Hereditary Leiomyomatosis [ICD-11: 2C90]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Tafazzin (TAFAZZIN) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
RCC4 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0498
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
HEK-293T cells Normal Homo sapiens CVCL_0063
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
In Vivo Model
One million 786O cells with or without shTAZ were implanted subcutaneously into the healthy 8-week-old JAX NOD.CB17-PrkdcSCID-J mice; both male and female mice were used. Once tumor volume reached 120 mm3, mice were randomized into control or erastin treatment group. The vehicle (ORA-plus) or erastin (0.1 ml of 4 mg/ml erastin) was administrated by oral gavage twice daily for 20 days.

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Response regulation Cell density-regulated ferroptosis is mediated by TAZ through the regulation of EMP1-NOX4, suggesting its therapeutic potential for renal cell carcinoma (RCC) and other TAZ-activated tumors.
References
Ref 1 The Hippo Pathway Effector TAZ Regulates Ferroptosis in Renal Cell Carcinoma. Cell Rep. 2019 Sep 3;28(10):2501-2508.e4. doi: 10.1016/j.celrep.2019.07.107.
Ref 2 YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis. EMBO Mol Med. 2021 Dec 7;13(12):e14351. doi: 10.15252/emmm.202114351. Epub 2021 Oct 19.