Comprehensive study for mitochondrial iron metabolism

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13680712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: YAMAGUCHI Yuko Graduate school of Biostudies, Associate Professor, 生命科学研究科, 助教授 (10281726)
• Project Period (FY): 2001 – 2002
• Keywords: mitochondria / iron-sulfer cluster / iron metabolism / thioredoxin / appotosis / DT40 / ROS

Research Abstract

Mitochondria play pivotal roles in iron metabolism in cells as the biosynthesis of heme and iron-sulfur cluster, the prosthetic groups of iron proteins, take place. In Sacckromyces cerevisiae, we found the activity of Aftl transcriptional activator, the major regulator of cellular iron metabolism, was affected by the aberration of mitochondrial iron metabolism. Based on this finding, we analyzed the mechanisms for regulating the activity of Aftl and its connection to the iron metabolism in mitochondria. Moreover, we cloned a battery of genes in chicken cells which are homologous to the ones expected to be involved in mitochondrial iron metabolism and established the cell line which is deficient in the relevant gene in chicken B cell line, DT40 to see how the deficiency of the relevant gene affects iron metabolism in mitochondria. We found that the NifS gene that is important for the formation of iron-sulfur cluster is essential for cell viability. In addition, we also established the mitochondrial thioredoxio, Trx-2 deficient cell line and found that loss of Trx-2 leads to apoptosis of cells partly due to the accumulation of reactive oxygen species (ROS) generated in Trx-2 deficient mitochondria

Research Products

• [Publications] Tanaka, T., Hosoi, F., Yamaguchi-Iwai, Y., et al.: "Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis"EMBO J.. 21. 1695-1703 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamaguchi-Iwai, Y., et al.: "Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae"J. Biol. Chem.. 277. 18914-18918 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kambe, T., Narita, H., Yamaguchi-Iwai, Y., et al.: "Cloning and characterization of a novel mammalian zinc transporter, ZnT-5, abundantly expressed in pancreatic beta cells"J. Biol. Chem.. 277. 19049-19055 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Furukawa, T., Adachi, Y., Fujisawa, J., Kambe, T., Yamaguchi-Iwai, Y., et al.: "Involvement of PLAGL2 in Activation of Iron Deficient-and Hypoxia-induced Gene Expression in Mouse Cell Lines"Oncogene. 20. 4718-4727 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Furukawa,T., Adachi,Y., Fujisawa,J., Kambe,T., Yamaguchi-Iwai,Y., Sasaki,R., Kuwahara,J., Dcehara,S., Tokunaga,R., and Taketani,S.: "Involvement of PLAGL2 in Activation of Iron Deficient- and Hypoxia-induced Gene Expression in Mouse Cell Lines"Oncogene. 20. 4718-4727 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tanaka,T., Hosoi,E., Yamaguchi-Iwai,Y., Nakamura,H., Masutani,H., Ueda,S., Nishiyama,A., Takeda,S., Wada,H., Spyrou,G., and Yodoi,J.: "Thioredoxin-2 (TRX-2) is anessential gene regulating mitochondria-dependent apoptosis"EMBO J.. 21. 1695-1703 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yamaguchi-Iwai,Y., Ueta,R., Fukunaka,A., and Sasaki,R.: "Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae"J. Biol Chem.. 277. 18914-18918 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kambe,T., Narita,T., Yamaguchi-Iwai,Y., Hirose,J., Aknano,T., Sugiura,N., Sasaki,R., Mori,K., Iwanaga,T., and Nagao,M.: "Cloning and characterization of a novel mammalian zinc transporter, ZnT-5, abundantly expressed in pancreatic beta cells"J. Biol. Chem.. 277. 19049-19055 (2002)
  • Description: 「研究成果報告書概要(欧文)」より