Analysis of mitochondrial functions in diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 22249018
• 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 九州大学, 医学研究院, 臨床検査医学 (80214716)
• Co-Investigator(Kenkyū-buntansha): KAYAMORI Yuzo 九州大学, 大学院・医学研究院, 教授 (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) ; TAKAZAKI Shinya 九州大学, 大学院・医学研究院, 助教 (90435149)
• Project Period (FY): 2010 – 2012
• 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

(1) ERAL1 and p32 of TFAM-binding proteins were essential for efficient formation of mitochondrial ribosomes, suggesting contribution of mitochondrial nucleoids to mitochondrial translation. (2) A metabolomic analysis system of cells harboring mitochondrial DNA mutations was set up. (3) Single nucleotide polymorphisms related to metabolic syndrome and Alzheimer disease were found.

Research Products

• [Journal Article] Protein instability and functional defect by mutations of dihydroorotate dehydrogenase with Miller syndrome patients (2012)
  • Author(s): Fang, J., Uchiumi, T., Yagi, M., Matsumoto, S., Amamoto, R., Saito, T., Takazaki, S., Kanki, T., Yamaza, H., Nonaka, K., Kang, D.
  • Journal Title: Biosci Rep. Volume: 32 Pages: 631-639
• [Journal Article] Dihydroorotate dehydrogenase is physically associated with the respiratory complex and its loss leads to mitochondrial dysfunction (2012)
  • Author(s): Fang, J., Uchiumi, T., Yagi, M., Matsumoto, S., Amamoto, R., Takazaki, S., Yamaza, H., Nonaka, K., Kang, D.
  • Journal Title: Biosci Rep.
• [Journal Article] Recombinant mitochondrial transcription factor A protein inhibits nuclear factor of activated T cells signaling and attenuates pathological hypertrophy of cardiac myocytes (2012)
  • Author(s): Fujino, T., Ide, T., Yoshida, M., Onitsuka, K., Tanaka, A., Hata, Y., Nishida, M., Takehara, T., Kanemaru, T., Kitajima, N., Takazaki, S., Kurose, H., Kang, D., Sunagawa, K.
  • Journal Title: Mitochondrion Volume: 12 Pages: 449-458
• [Journal Article] Mitophagy plays an essential role in reducing mitochondrial production of reactive oxygen species and mutation of mitochondrial DNA by maintaining mitochondrial quantity and quality in yeast (2012)
  • Author(s): Kurihara, Y., Kanki, T., Aoki, Y., Hirota, Y., Saigusa, T., Uchiumi, T., Kang, D.
  • Journal Title: J Biol Chem Volume: 287 Pages: 3265-72
• [Journal Article] Localization of mRNAs encoding human mitochondrial oxidative phosphorylation proteins (2012)
  • Author(s): Matsumoto, S., Uchiumi, T., Saito, T., Yagi, M., Takazaki, S., Kanki, T., Kang, D.
  • Journal Title: Mitochondrion Volume: 12 Pages: 391-398
• [Journal Article] Ribonucleoprotein Y-box-binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA (2012)
  • Author(s): Matsumoto, S., Uchiumi, T., Tanamachi, H., Saito, T., Yagi, M., Takazaki, S., Kanki, T., Kang, D.
  • Journal Title: Biochem J. Volume: 443 Pages: 573-84
• [Journal Article] Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice (2012)
  • Author(s): Oba, T., Yasukawa, H., Hoshijima, M., Sasaki, K., Futamata, N., Fukui, D., Mawatari, K., Nagata, T., Kyogoku, S., Ohshima, H., Minami, T., Nakamura, K., Kang, D., Yajima, T., Knowlton, K. U., Imaizumi, T.
  • Journal Title: J Neurosci Res. Volume: 90 Pages: 1200-8
• [Journal Article] Cardiac-specific deletion of SOCS-3 prevents development of left ventricular remodeling after acute myocardial infarction (2012)
  • Author(s): Oba, T., Yasukawa, H., Hoshijima, M., Sasaki, K., Futamata, N., Fukui, D., Mawatari, K., Nagata, T., Kyogoku, S., Ohshima, H., Minami, T., Nakamura, K., Kang, D., Yajima, T., Knowlton, K. U., Imaizumi, T.
  • Journal Title: J Am Coll Cardiol Volume: 59 Pages: 838-52
• [Journal Article] Arg 901 in the AE1 C-terminal tail is involved in conformational change but not in substrate binding (2012)
  • Author(s): Takazaki, S., Abe, Y., Yamaguchi, T., Yagi, M., Ueda, T., Kang, D., Hamasaki, N
  • Journal Title: Biochim Biophys Acta. Volume: 1818 Pages: 658-65
• [Journal Article] mtSSB may sequester UNG1 at mitochondrial ssDNA and delay uracil processing until the dsDNA conformation is restored (2012)
  • Author(s): Wollen Steen, K., Doseth, B., M, P. W., Akbari, M., Kang, D., Falkenberg, M., Slupphaug, G
  • Journal Title: DNA Repair (Amst) Volume: 11 Pages: 82-91
• [Journal Article] p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability (2012)
  • Author(s): Yagi, M., Uchiumi, T., Takazaki, S., Okuno, B., Nomura, M., Yoshida, S. I., Kanki, T., Kang, D
  • Journal Title: Nucleic Acids Res. Volume: 40 Pages: 9717-9737
• [Journal Article] Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter prostate-specific antigen relapse time after radical prostatectomy (2011)
  • Author(s): Amamoto, R., Yagi, M., Song, Y., Oda, Y., Tsuneyoshi, M., Naito, S., Yokomizo, A., Kuroiwa, K., Tokunaga, S., Kato, S., Hiura, H., Samori, T., Kang, D., Uchiumi, T.
  • Journal Title: Cancer Sci. Volume: 102 Pages: 639-47
• [Journal Article] Phosphorylation of Serine 114 on Atg32 mediates mitophagy (2011)
  • Author(s): Aoki, Y., Kanki, T., Hirota, Y., Kurihara, Y., Saigusa, T., Uchiumi, T., Kang, D.
  • Journal Title: Mol Biol Cell Volume: 22 Pages: 3206-17
• [Journal Article] Frequent Truncating Mutation of TFAM Induces Mitochondrial DNA Depletion and Apoptotic Resistance in Microsatellite-Unstable Colorectal Cancer (2011)
  • Author(s): Guo, J., Zheng, L., Liu, W., Wang, X., Wang, Z., Wang, Z., French, A. J., Kang, D., Chen, L., Thibodeau, S. N., Liu, W.
  • Journal Title: Cancer Res Volume: 71 Pages: 2978-87
• [Journal Article] 1,2-Dioleoylglycerol method for pancreatic lipase catalytic activity in serum (2011)
  • Author(s): Iizuka, Y., Ueda, S., Hanada, T., Tani, W., Adachi, H., Haga, R., Yamaguchi, M., Kurotani, W., Sekiguchi, M., Kang, D., Sakasegawa, S.
  • Journal Title: Clin Chem Lab Med Volume: 50 Pages: 475-81
• [Journal Article] IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. (2011)
  • Author(s): Schumann, G., Klauke, R., Canalias, F., Bossert-Reuther, S., Franck, P. F., Gella, F. J., Jorgensen, P. J., Kang, D., Lessinger, J. M., Panteghini, M., Ceriotti, F.
  • Journal Title: Clin Chem Lab Med Volume: 49 Pages: 1439-46
• [Journal Article] Mitochondrial single-stranded DNA binding protein is required for maintenance of mitochondrial DNA and 7S DNA but is not required for mitochondrial nucleoid organisation (2010)
  • Author(s): Ruhanen, H., Borrie, S., Szabadkai, G., Tyynismaa, H., Jones, A. W., Kang, D., Taanman, J. W., Yasukawa, T
  • Journal Title: Biochim Biophys Acta Volume: 1803 Pages: 931-939
• [Journal Article] IFCC reference procedures for measurement of the catalytic concentrations of enzymes: corrigendum, notes and useful advice (2010)
  • Author(s): Schumann, G., Canalias, F., Joergensen, P. J., Kang, D., Lessinger, J. M., Klauke, R
  • Journal Title: Clin Chem Lab Med Volume: 48 Pages: 615-21
• [Journal Article] PLEDs in an infant with congenital protein C deficiency: a case report (2010)
  • Author(s): Sekiguchi, K., Akiyoshi, K., Okazaki, N., Yamada, H., Suzuki, M., Maeda, T., Suenobu, S., Izumi, T., Kang, D
  • Journal Title: Clin Neurophysiol Volume: 121 Pages: 800-1
• [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 Volume: 1798 Pages: 903-908
• [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 Volume: 35 Pages: 444-50
• [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. Volume: 35 Pages: 387-91
• [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. Volume: 38 Pages: 5554-5568
• [Journal Article] Helical image reconstruction of the outward-open human erythrocyte band 3 membrane domain in tubular crystals (2010)
  • Author(s): Yamaguchi, T., Fujii, T., Abe, Y., Hirai, T., Kang, D., Namba, K., Hamasaki, N., Mitsuoka, K.
  • Journal Title: J Struct Biol. Volume: 169 Pages: 406-412
• [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. Volume: 397 Pages: 179-89
• [Presentation] RNA-binding proteins involved in mitochondrial proteins synthesis (2012)
  • Author(s): D. Kang
  • Organizer: 7th International Symposium on Genomic Medicine of CCH (Joint Symposium of Taiwan Society for Mitochondrial Research and Medicine/ Australasian College of Medical Sciences and Research) 2012
  • Place of Presentation: Taichung, Taiwan
  • Year and Date: 20121026-27
• [Presentation] ミトコンドリアゲノムの維持とヒトの疾患:活性酸素とTFAMの意義(WS「ミトコンドリアゲノムが制御する多様な生命現象」) (2012)
  • Author(s): 康東天
  • Organizer: 第84回日本遺伝学会大会
  • Place of Presentation: 福岡
  • Year and Date: 20120924-26
• [Presentation] 老化におけるミトコンドリアとTFAM(シンポジウム「身から出た錆:ミトコンドリアから長寿を科学する」) (2012)
  • Author(s): 康東天
  • Organizer: 第12回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20120622-24
• [Presentation] ミトコンドリアゲノムと酸化ストレス:TFAMから見る細胞機能 (2012)
  • Author(s): 康東天
  • Organizer: 第22回生物試料分析科学会年次学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120310-11
• [Presentation] Implications of mitochondrial oxidative stress in common diseases (2012)
  • Author(s): D. Kang
  • Organizer: International symposium of mitochondrial biomedicine & ASMRM Council Meeting
  • Place of Presentation: Hangzhou, China
  • Year and Date: 2012-04-08
• [Presentation] Importance of Mitochondrial genome in cellular functions:Oxidative stress and TFAM (2011)
  • Author(s): D. Kang
  • Organizer: Mckay International symposium 0n mitochondrial medicine in human health and diseases
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2011-07-09
• [Book] Cellular and Genetic Practices for Translational Medicine Research (2011)
  • Author(s): Kang, D
  • Publisher: Importance of mitochondrial genome in multiple cellular functions: A central role of TFAM in its maintenance
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/cclm/