Mitochondrial DNA disease and its diagnostic system

• Project/Area Number: 19209019
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kyushu University
• Principal Investigator: KANG Dongchon Kyushu University, 大学院・医学研究院, 教授 (80214716)
• Co-Investigator(Kenkyū-buntansha): KAYAMORI Yuzo 九州大学, 大学病院, 技師長 (90398066) ; UCHIUMI Takeshi 九州大学, 大学院・医学研究院, 准教授 (80253798) ; KANKI Tomotake 九州大学, 大学病院, 助教 (50398088) ; FUKUOH Atsushi 九州大学, 大学病院, 助教 (80363365) ; TAKAYANAGI Ryoichi 九州大学, 大学院・医学研究院, 教授 (30154917) ; KONO Suminori 九州大学, 大学院・医学研究院, 教授 (70128015)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥50,440,000 (Direct Cost: ¥38,800,000、Indirect Cost: ¥11,640,000); Fiscal Year 2009: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2008: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000); Fiscal Year 2007: ¥26,390,000 (Direct Cost: ¥20,300,000、Indirect Cost: ¥6,090,000)
• Keywords: ミトコンドリアDNA / 遺伝子診断 / 活性酸素 / 糖尿病 / ミトコンドリア病 / 遺伝子多型 / 老化

Research Abstract

The following three projects are integrated for further understanding of mitochondrial disease and for construction of its diagnostic system : (1) molecular mechanism of maintenance of mitochondrial DNA (mtDNA), (2) molecular diagnosis of mitochondrial disease, and (3) mtDNA analysis of somatic cells. Now we accept genetic tests of mitochondrial disease from all over Japan. During this period, we have shown that maintenance of mtDNA can delay natural aging process in TFAM-expressing transgenic mice. The mtDNA analysis of somatic cells is on going.

Research Products

• [Journal Article] IFCC reference procedures for catalytic concentration measurement of enzymes: Corrigendum, notes and useful advice. (2010)
  • Author(s): Schumann, G., Canalias, F., Joergensen, P.J., Kang, D., Klauke, R.
  • Journal Title: Clin. Chem. Lab. Med. 48 Pages: 615-621
  • Peer Reviewed
• [Journal Article] Sorafenib with doxorubicin augments cytotoxicity to renal cell cancer through PERK inhibition. (2010)
  • Author(s): Shiota, M., Eto, M., Yokomizo, A., Tada, Y., Takeuchi, A., Masubuchi, D., Inokuchi, J., Tatsugami, K., Kuroiwa, K., Uchiumi, T., et al.
  • Journal Title: Int J Oncol 36 Pages: 1521-1531
  • Peer Reviewed
• [Journal Article] Human heterochromatin protein 1 isoform HP1{beta} enhances androgen receptor activity and is implicated in prostate cancer growth. (2010)
  • Author(s): Shiota, M., Song, Y., Yokomizo, A., Tada, Y., Kuroiwa, K., Eto, M., Oda, Y., Inokuchi, J., Uchiumi, T., Fujimoto, N., et al.
  • Journal Title: Endocr Relat Cancer
  • Peer Reviewed
• [Journal Article] Foxo3a expression and acetylation regulate cancer cell growth and sensitivity to cisplatin. (2010)
  • Author(s): Shiota, M., Yokomizo, A., Kashiwagi, E., Tada, Y., Inokuchi, J., Tatsugami, K., Kuroiwa, K., Uchiumi, T., Seki, N., Naito, S.
  • Journal Title: Cancer Sci.
  • NAID: 10026592158
  • Peer Reviewed
• [Journal Article] Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus. (2010)
  • Author(s): Shiota, M., Yokomizo, A., Masubuchi, D., Tada, Y., Inokuchi, J., Eto, M., Uchiumi, T., Fujimoto, N., Naito, S.
  • Journal Title: Prostate 70 Pages: 540-554
  • Peer Reviewed
• [Journal Article] Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression. (2010)
  • Author(s): Shiota, M., Yokomizo, A., Tada, Y., Inokuchi, J., Kashiwagi, E., Masubuchi, D., Eto, M., Uchiumi, T., Naito, S.
  • Journal Title: Oncogene 29 Pages: 237-250
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor gamma coactivator-1alpha interacts with the androgen receptor (AR) and promotes prostate cancer cell growth by activating the AR. (2010)
  • Author(s): Shiota, M., Yokomizo, A., Tada, Y., Inokuchi, J., Tatsugami, K., Kuroiwa, K., Uchiumi, T., Fujimoto, N., Seki, N., Naito, S.
  • Journal Title: Mol Endocrinol 24 Pages: 114-127
  • Peer Reviewed
• [Journal Article] Mutation of His 834 in human anion exchanger 1 affects substrate binding. (2010)
  • Author(s): Takazaki, S., Abe, Y., Yamaguchi, T., Yagi, M., Ueda, T., Kang, D., Hamasaki, N.
  • Journal Title: Biochim Biophys Acta 1798 Pages: 903-908
  • Peer Reviewed
• [Journal Article] ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation. (2010)
  • Author(s): Uchiumi, T., Ohgaki, K., Yagi, M., Aoki, Y., Sakai, A., Matsumoto, S., Kang, D.
  • Journal Title: Nucleic Acids Res.
  • NAID: 120005227389
  • Peer Reviewed
• [Journal Article] Helical image reconstruction of the outward-open human erythrocyte band 3 membrane domain in tubular crystals. (2010)
  • Author(s): amaguchi, T., Fujii, T., Abe, Y., Hirai, T., Kang, D., Namba, K., Hamasaki, N., Mitsuoka, K.
  • Journal Title: J Struct Biol 169 Pages: 406-412
  • Peer Reviewed
• [Journal Article] Structure of the membrane domain of human erythrocyte anion exchanger 1 revealed by electron crystallography. (2010)
  • Author(s): Yamaguchi, T., Ikeda, Y., Abe, Y., Kuma, H., Kang, D., Hamasaki, N., Hirai, T.
  • Journal Title: J Mol Biol 397 Pages: 179-189
  • Peer Reviewed
• [Journal Article] Clonal spread in Eastern Asia of ciprofloxacin-resistant Escherichia coli serogroup O25 strains, and associated virulence factors. (2010)
  • Author(s): Uchida, Y., Mochimaru, T., Morokuma, Y., Kiyosuke, M., Fujise, M., Eto, F., Eriguchi, Y., Nagasaki, Y., Shimono, N., Kang, D.
  • Journal Title: Int J Antimicrob Agents 35 Pages: 444-450
  • Peer Reviewed
• [Journal Article] Geographic distribution of fluoroquinolone-resistant Escherichia coli strains in Asia. (2010)
  • Author(s): Uchida, Y., Mochimaru, T., Morokuma, Y., Kiyosuke, M., Fujise, M., Eto, F., Harada, Y., Kadowaki, M., Shimono, N., Kang, D.
  • Journal Title: Int J Antimicrob Agents 35 Pages: 387-391
  • Peer Reviewed
• [Journal Article] Mutation of His 834 in human anion exchanger 1 affects substrate binding. Biochim (2010)
  • Author(s): Takazaki, S., et al.
  • Journal Title: Biochim Biophys Acta, 1798, Pages: 903-908
  • Peer Reviewed
• [Journal Article] Helical image reconstruction of the outward-open human erythrocyte band 3 membrane domain in tubular crystals. (2010)
  • Author(s): Yamaguchi, T., et al.
  • Journal Title: J Struct Biol, 169, Pages: 406-412
  • Peer Reviewed
• [Journal Article] Structure of the membrane domain of human erythrocyte anion exchanger 1 revealed by electron crystallography. (2010)
  • Author(s): Yamaguchi, T., et al.
  • Journal Title: J Mol Biol, 397, Pages: 179-189
  • Peer Reviewed
• [Journal Article] DNA conformation-dependent activities of human mitochondrial RNA polymerase. (2009)
  • Author(s): Fukuoh, A., Ohgaki, K., Hatae, H., Kuraoka, I., Aoki, Y., Uchiumi, T., Jacobs, H.T., Kang, D.
  • Journal Title: Genes Cells 14 Pages: 1029-1042
  • Peer Reviewed
• [Journal Article] Development of a new measurement method for serum calcium with chlorophosphonazo-III. (2009)
  • Author(s): Hokazono, E., Osawa, S., Nakano, T., Kawamoto, Y., Oguchi, Y., Hotta, T., Kayamori, Y., Kang, D., Cho, Y., Shiba, K., et al.
  • Journal Title: Ann Clin Biochem 46 Pages: 296-301
  • Peer Reviewed
• [Journal Article] Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy. (2009)
  • Author(s): Ishimura, M., Saito, M., Ohga, S., Hoshina, T., Baba, H., Urata, M., Kira, R., Takada, H., Kusuhara, K., Kang, D., et al.
  • Journal Title: Eur J Pediatr 168 Pages: 673-677
• [Journal Article] Atg32 is a mitochondrial protein that confers selectivity during mitophagy. (2009)
  • Author(s): Kanki, T., Wang, K., Cao, Y., Baba, M., Klionsky, D.J.
  • Journal Title: Dev Cell 17 Pages: 98-109
  • Peer Reviewed
• [Journal Article] A genomic screen for yeast mutants defective in selective mitochondria autophagy. (2009)
  • Author(s): Kanki, T., Wang, K., Baba, M., Bartholomew, C.R., Lynch-Day, M.A., Du, Z., Geng, J., Mao, K., Yang, Z., Yen, W.L., et al.
  • Journal Title: Mol Biol Cell 20 Pages: 4730-4738
  • Peer Reviewed
• [Journal Article] High-dose penicillin G-treatment causes underestimation of serum albumin measured by a modified BCP method. (2009)
  • Author(s): Ono, M., Aoki, Y., Masumoto, M., Hotta, T., Uchida, Y., Kayamori, Y., Kang, D.
  • Journal Title: Clin. Chim. Acta 407 Pages: 75-76
  • Peer Reviewed
• [Journal Article] Human heart mitochondrial DNA is organized in complex catenated networks containing abundant four-way junctions and replication forks. (2009)
  • Author(s): Pohjoismaki, J.L., Goffart, S., Tyynismaa, H., Willcox, S., Ide, T., Kang, D., Suomalainen, A., Karhunen, P.J., Griffith, J.D., Holt, I.J., et al.
  • Journal Title: J Biol Chem 284 Pages: 21446-21457
  • Peer Reviewed
• [Journal Article] Association of a novel mitochondrial protein M19 with mitochondrial nucleoids. (2009)
  • Author(s): Sumitani, M., Kasashima, K., Ohta, E., Kang, D., Endo, H.
  • Journal Title: J Biochem 146 Pages: 725-732
  • Peer Reviewed
• [Journal Article] Methods for Assessing Binding of Mitochondrial Transcription Factor A (TFAM) to DNA. (2009)
  • Author(s): Fukuoh, A., Kang, D.
  • Journal Title: Methods Mol Biol 554 Pages: 87-101
  • Peer Reviewed
• [Journal Article] Monitoring mitophagy in yeast: the Om45-GFP processing assay. (2009)
  • Author(s): Kanki, T., Kang, D., Klionsky, D.J.
  • Journal Title: Autophagy 5 Pages: 1186-1189
  • Peer Reviewed
• [Journal Article] DNA conformation-dependent activities of human mitochondrial RNA polymerase. (2009)
  • Author(s): Fukuoh, A., et al.
  • Journal Title: Genes Cells, 14, Pages: 1029-1042
  • Peer Reviewed
• [Journal Article] Development of a new measurement method for serum calcium with chlorophosphonazo-III. (2009)
  • Author(s): Hokazono, E., et al.
  • Journal Title: Ann Clin Biochem, 46, Pages: 296-301
  • Peer Reviewed
• [Journal Article] Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy. (2009)
  • Author(s): Ishimura, M., et al.
  • Journal Title: Eur J Pediatr, 168, Pages: 673-677
  • Peer Reviewed
• [Journal Article] High-dose penicillin G-treatment causes underestimation of serum albumin measured by a modified BCP method. (2009)
  • Author(s): Ono, M., et al.
  • Journal Title: Clin. Chim. Acta, 407, Pages: 75-76
  • Peer Reviewed
• [Journal Article] Human heart mitochondrial DNA is organized in complex catenated net works containing abundant four-way junctions and replication forks. (2009)
  • Author(s): Pohjoismaki, J.L., et al.
  • Journal Title: J Biol Chem, 284 Pages: 21446-21457
  • Peer Reviewed
• [Journal Article] Association of a novel mitochondrial protein M19 with mitochondrial nucleoids. (2009)
  • Author(s): Sumitani, M., et al.
  • Journal Title: J Biochem, 146, Pages: 725-732
  • Peer Reviewed
• [Journal Article] Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy (2009)
  • Author(s): Ishimura, M., et al.
  • Journal Title: Eur J Pediatr (In press)
  • Peer Reviewed
• [Journal Article] Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice. (2008)
  • Author(s): Hayashi, Y., Yoshida, M., Yamato, M., Ide, T., Wu, Z., Ochi-Shindou, M., Kanki, T., Kang, D., Sunagawa, K., Tsutsui, H., et al.
  • Journal Title: J Neurosci 28 Pages: 8624-8634
  • Peer Reviewed
• [Journal Article] Decreased maternal protein S activity is associated with fetal growth restriction. (2008)
  • Author(s): Hojo, S., Tsukimori, K., Kinukawa, N., Hattori, S., Kang, D., Hamasaki, N., Wake, N.
  • Journal Title: Thromb Res 123 Pages: 55-59
  • Peer Reviewed
• [Journal Article] Thromboembolic Complications in Splenectomized Patients with Dominantly Inherited beta-Thalassemia. (2008)
  • Author(s): Ohga, S., Ideguchi, H., Kato, J., Ishimura, M., Takada, H., Harada, N., Kawanaka, H., Hattori, Y., Kang, D., Hamasaki, N., et al.
  • Journal Title: Acta Haematol 120 Pages: 31-35
  • Peer Reviewed
• [Journal Article] Platelet contamination causes large variation as well as overestimation of mitochondrial DNA content of peripheral blood mononuclear cells. (2008)
  • Author(s): Urata, M., Koga-Wada, Y., Kayamori, Y., Kang, D.
  • Journal Title: Ann Clin Biochem 45 Pages: 513-514
  • Peer Reviewed
• [Journal Article] Platelet contamination causes large variation as well as overestimation of mitochondrial DNA content of peripheral blood monon uclear cells. (2008)
  • Author(s): Urata, M., et al.
  • Journal Title: Ann Clin Biocbem 45 Pages: 513-514
  • Peer Reviewed
• [Journal Article] Thromboembolic Complications in Splenectomized Patients with Dominantly Inherited beta-Thalassemia (2008)
  • Author(s): Ohga, S., et al.
  • Journal Title: Acta Haematol 120 Pages: 31-35
  • Peer Reviewed
• [Journal Article] Decreased maternal protein S activity is associated with fetal growth restriction. (2008)
  • Author(s): Hojo, S., et al.
  • Journal Title: Thromb Res 123 Pages: 55-59
  • Peer Reviewed
• [Journal Article] Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice. (2008)
  • Author(s): Hayashi, Y., et al.
  • Journal Title: J Neurosci 28 Pages: 8624-8634
  • Peer Reviewed
• [Journal Article] Decreased maternal protein S activity is associated with fetal growth restriction (2008)
  • Author(s): Satoshi H., et. al.
  • Journal Title: Thrombosis Research (In press)
  • Peer Reviewed
• [Journal Article] Platelet contamination causes large cariation as well as overestimation of mitochomdrial DNA content of peripheral blood mononuclear cells (2008)
  • Author(s): Urata, M., et. al.
  • Journal Title: Annals of Clinical Biochemistry (In press)
  • Peer Reviewed
• [Journal Article] The C-terminal tail of mitochondrial transcription factor a markedly strengthens its general binding to DNA. (2007)
  • Author(s): Ohgaki, K., Kanki, T., Fukuoh, A., Kurisaki, H., Aoki, Y., Ikeuchi, M., Kim, S.H., Hamasaki, N., Kang, D.
  • Journal Title: J Biochem 141 Pages: 201-211
  • NAID: 10020101269
  • Peer Reviewed
• [Journal Article] Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. (2007)
  • Author(s): Kang, D., Kim, S.H., Hamasaki, N.
  • Journal Title: Mitochondrion 7 Pages: 39-44
  • Peer Reviewed
• [Journal Article] The C-terminal tail of mitochondrial transcription factor a markedly strengthen its general binding to DNA (2007)
  • Author(s): Ohgaki, K., et. al.
  • Journal Title: J Biochem 141 Pages: 201-211
  • Peer Reviewed
• [Journal Article] Mitochondrial transcription factor A (TFAM):roles in maintenance of mtDNA and cellular functions (2007)
  • Author(s): Kang, D., et. al.
  • Journal Title: Mitochondrion 7 Pages: 39-44
  • Peer Reviewed
• [Presentation] Mitochondria: genome and ROS (2009)
  • Author(s): D. Kang
  • Organizer: Summer School of Society of Free Radical Research International
  • Place of Presentation: Niigata
• [Presentation] Importance of Mitochondrial Genome in Cellular Functions (2009)
  • Author(s): D. Kang
  • Organizer: The 21st Annual Meeting of the Korean Society of Molecular and Cellular Biology
  • Place of Presentation: Seoul, Korea
• [Presentation] Promoter-independent RNA synthesis activity of human mitochondrial RNA polymerase (2008)
  • Author(s): D. Kang
  • Organizer: The 7th European Meeting on Mitochondrial Pathology
  • Place of Presentation: Stockholm, Sweden
• [Presentation] Primase-like function of Mitochondrial RNA Polymerase (2007)
  • Author(s): D. Kang
  • Organizer: ScandoMit2007
  • Place of Presentation: Teisko, Finland
• [Presentation] Importance of mtDNA Nucleoid in Maintenance of mtDNA and Prevention of Apoptosis (2007)
  • Author(s): D. Kang
  • Organizer: The 4th Conference of the Asian Society for Mitochondrial Research and Medicine
  • Place of Presentation: Seoul Korea
• [Remarks] ホームページ
  • URL: http://www.med.kyushu-u.ac.jp/cclm/
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/cclm/kyositu/index.html