Mitochondrial DNA analysis for Alzheimer disease cohort study

• Project/Area Number: 24659281
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kyushu University
• Principal Investigator: KANG DONGCHON 九州大学, 医学(系)研究科(研究院), 教授 (80214716)
• Co-Investigator(Renkei-kenkyūsha): KIYOHARA Yutaka 九州大学, 大学院医学研究科, 教授 (80161602)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ミトコンドリアDNA / アルツハイマー病 / コホート研究 / アルツハイマー / ミトコンドリアゲノム / メタボローム / コホート / ミトコンドリアＤＮＡ

Outline of Final Research Achievements

The mitochondrial DNA sequences in the two regions (D-loop and ND6) have been determined for about 1.5 thousand residents in Hisayama town, Fukuoka prefecture. We have found thatone single nucleotide polymorphism (SNP) is statistically linked to Alzheimer disease. We are planning to establish the cybrid cell lines which contain the SNP and to analyze their mitochondrial activities, energy metabolism, and so on.

Research Products

• [Journal Article] Improvement and evaluation of a 1,2-dioleoylglycerol method for measuring pancreatic lipase catalytic activity in serum, (2014)
  • Author(s): Iizuka, Y., Yamashita, K., Sakasegawa, S., Hanada, T., Tani, W., Adachi, H., Haga, R., Yamaguchi, M., Kurotani, W., Sekiguchi, M., Osawa, S., Hosogaya, S., Kang, D., Ueda, S.
  • Journal Title: Clin. Chem. Lab. Med Volume: 52 Pages: 171-173
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tor and the Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32 in yeast. (2014)
  • Author(s): Aihara M, Jin X, Kurihara Y, Yoshida Y, Matsushima Y, Oku M, Hirota Y, Saigusa T, Aoki Y, Uchiumi T, Yamamoto T, Sakai Y, Kang D, Kanki T.
  • Journal Title: Journal of Cell Science Volume: 127 Pages: 3184-96
  • DOI: 10.1242/jcs.153254
  • Peer Reviewed / Open Access
• [Journal Article] A novel mutation in protein C gene (PROC) causing severe phenotype in neonatal period, Pediatr (2014)
  • Author(s): Unal, S., Gumruk, F., Yigit, S., Tuncer, M., Tavil, B., Cil, O., Takci, S., Urata, M., Hotta, T., Kang, D., Cetin, M.
  • Journal Title: Blood Cancer Volume: 61 Issue: 4 Pages: 763-764
  • DOI: 10.1002/pbc.24782
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: the Hisayama Study. (2014)
  • Author(s): Mukai N, Yasuda M, Ninomiya T, Hata J, Hirakawa Y, Ikeda F, Fukuhara M, Hotta T, Koga M, Nakamura U, Kang D, Kitazono T, Kiyohara Y.
  • Journal Title: Cardiovasc Diabetol Volume: 13 Issue: 1 Pages: 45-45
  • DOI: 10.1186/1475-2840-13-45
  • Peer Reviewed / Open Access
• [Journal Article] Staphylococcal endocarditis as the first manifestation of heritable protein S deficiency in childhood, (2014)
  • Author(s): Hoshina, T., Nakashima, Y., Sato, D., Nanishi, E., Nishio, H., Nagata, H., Yamamura, K., Doi, T., Shiokawa, Y., Koga, Y., Kang, D., Ohga, S., Hara, T.
  • Journal Title: J. Infect. Chemother Volume: 20 Issue: 2 Pages: 128-130
  • DOI: 10.1016/j.jiac.2013.08.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1, (2014)
  • Author(s): Baba, T., Otake, H., Sato, T., Miyabayashi, K., Shishido, Y., Wang, C. Y., Shima, Y., Kimura, H., Yagi, M., Ishihara, Y., Hino, S., Ogawa, H., Nakao, M., Yamazaki, T., Kang, D., Ohkawa, Y., Suyama, M., Chung, B. C., Morohashi, K.
  • Journal Title: Nat. Commun Volume: 5 Pages: 3634-3634
  • NAID: 130005085557
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Casein kinase 2 is essential for mitophagy. (2013)
  • Author(s): Kanki T., Kurihara Y., Jin X., Goda T., Ono Y., Aihara M., Hirota Y., Saigusa T., Aoki Y., Uchiumi T., Kang D.
  • Journal Title: EMBO reports Volume: 14巻 Issue: 9 Pages: 788-794
  • DOI: 10.1038/embor.2013.114
  • Peer Reviewed
• [Journal Article] Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster (2013)
  • Author(s): Matsuda T, Kanki T, Tanimura T, Kang D, Matsuura ET
  • Journal Title: Biochem Biophys Res Commun Volume: 430(2) Issue: 2 Pages: 717-21
  • DOI: 10.1016/j.bbrc.2012.11.084
  • Peer Reviewed
• [Journal Article] Effects of DNA lesions on the transcription reaction of mitochondrial RNA polymerase: implications for bypass RNA synthesis on oxidative DNA lesions, (2013)
  • Author(s): Nakanishi, N., Fukuoh, A., Kang, D., Iwai, S.Kuraoka, I.
  • Journal Title: Mutagenesis Volume: 28 Issue: 1 Pages: 117-123
  • DOI: 10.1093/mutage/ges060
  • Peer Reviewed
• [Journal Article] Protein C deficiency as the major cause of thrombophilias in childhood, (2013)
  • Author(s): Ohga, S., Ishiguro, A., Takahashi, Y., Shima, M., Taki, M., Kaneko, M., Fukushima, K., Kang, D.Hara, T
  • Journal Title: ediatrics international : official journal of the Japan Pediatric Society Volume: 55 Issue: 3 Pages: 267-271
  • DOI: 10.1111/ped.12102
  • Peer Reviewed
• [Journal Article] Mutation and functional analysis of ABCC2/multidrug resistance protein 2 in a Japanese patient with Dubin-Johnson syndrome (2013)
  • Author(s): Uchiumi T, Tanamachi H, Kuchiwaki K, Kajita M, Matsumoto S, Yagi M, Kanki T, Kang D
  • Journal Title: Hepatol Res Volume: 43(5) Issue: 5 Pages: 569-75
  • DOI: 10.1111/j.1872-034x.2012.01103.x
  • NAID: 10031183491
  • Peer Reviewed
• [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: Bioscience reports Volume: 33 Issue: 2 Pages: 217-227
  • DOI: 10.1042/bsr20120097
  • Peer Reviewed
• [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, Kanki T, Kang D
  • Journal Title: Nuc Acid Res Volume: 19 Issue: 19 Pages: 9717-37
  • DOI: 10.1093/nar/gks774
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Arg901 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, Kagn D, Hamasaki N
  • Journal Title: Biochem.Biophy.Acta Volume: 1819 Issue: 3 Pages: 658-665
  • DOI: 10.1016/j.bbamem.2011.11.019
  • Peer Reviewed
• [Journal Article] Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice (2012)
  • Author(s): Morimoto, N., Miyazaki, K., Kurata, T., Ikeda, Y., Matsuura, T., Kang, D., Ide, T., Abe, K.
  • Journal Title: J Neurosci Res Volume: 90 Pages: 1200-1208
  • Peer Reviewed
• [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, et al
  • Journal Title: Biochemical J Volume: 443 Issue: 2 Pages: 573-584
  • DOI: 10.1042/bj20111728
  • Peer Reviewed
• [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(3) Issue: 3 Pages: 391-8
  • DOI: 10.1016/j.mito.2012.02.004
  • Peer Reviewed
• [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 Issue: 5 Pages: 3265-3272
  • DOI: 10.1074/jbc.m111.280156
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Protein instability and functional defects caused by mutations of dihydro-orotate dehydrogenase in 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: Bioscience reports Volume: 32 Pages: 631-639
  • Peer Reviewed
• [Journal Article] The role of TFAM-associated proteins in mitochondrial RNA metabolism, (2012)
  • Author(s): Uchiumi, T., Kang, D.
  • Journal Title: Biochimica et biophysica acta. Volume: 1820 Pages: 565-570
  • Peer Reviewed
• [Journal Article] Mitochondrial Genomic Disintegrity and Age-Related Diseases (2012)
  • Author(s): Kang, D.
  • Journal Title: Anti-Aging Medicine Volume: 9 Pages: 201-206
  • Peer Reviewed
• [Journal Article] The physiological role of mitophagy: new insights into phosphorylation events. (2012)
  • Author(s): Hirota, Y., Kang, D., Kanki, T.
  • Journal Title: International journal of cell biology Volume: 2012 Pages: 354914-354914
  • DOI: 10.1155/2012/354914
  • Peer Reviewed
• [Presentation] Brain－ and heart-specific disruption of p32 gene in mice causes vacuolar degenereation in mid-brain and dilated cardiomyopathy (2014)
  • Author(s): Kang, Dongchon
  • Organizer: The 9th International Symposium of Genomic Medicine
  • Place of Presentation: Changhua, Taiwan
  • Year and Date: 2014-11-15 – 2014-11-16
  • Invited
• [Presentation] Tissue specific KO mice of p32/gC1qR, a mitochondrial RNA chaperone (2014)
  • Author(s): Kang, Dongchon
  • Organizer: The 11th Conference of Asian Society for Mitochondrial Research and Medicine
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2014-11-14 – 2014-11-15
  • Invited
• [Presentation] 細胞と個体におけるミトコンドリアの形成と維持機能 (2014)
  • Author(s): 康 東天
  • Organizer: 第87回日本生化学大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] 血清脂質の基準範囲を考える (2014)
  • Author(s): 康 東天
  • Organizer: 第54回日本臨床化学会年次学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-05 – 2014-09-07
  • Invited
• [Presentation] ミトコンドリア生物学からミトコンドリア疾患学へ (2014)
  • Author(s): 康 東天
  • Organizer: 第87回日本内分泌学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] REAL1 and p32:factors for mitochondrial ribosome assembly (2013)
  • Author(s): Kang, Dongchon
  • Organizer: The 10th Conference of the Asian Society of Mitochondrial Research and Medicine(A-mit)
  • Place of Presentation: Grand Hilton Seoul Hotel
  • Invited
• [Presentation] 臨床検査医/検査部長の立場から望むこと：臨床検査学サイエンティストの養成 (2013)
  • Author(s): 康 東天
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸国際会議場
  • Invited
• [Presentation] 項目コード（JLAC10)を用いた多施設間検査情報のための取り組みと問題点 (2013)
  • Author(s): 康 東天
  • Organizer: 第60回日本臨床検査医学会学術集会
  • Place of Presentation: 神戸国際会議場,
  • Invited
• [Presentation] Implications of Mitochondrial Oxidative Stress in Common Diseases, (2012)
  • Author(s): Kang, D.
  • Organizer: International symposium of mitochondrial biomedicine & ASMRM Council Meeting.
  • Place of Presentation: Hangzhou, China
  • Invited
• [Presentation] Rna-Binding Proteins Involved in Mitochondrial Proteins Synthesis, (2012)
  • Author(s): Kang, D.
  • Organizer: 7th International Symposium on Genomic Medicine of CCH
  • Place of Presentation: Taichung, Taiwan
  • Invited
• [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
  • Invited
• [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
  • Invited
• [Presentation] 検査データの現状と課題（大会企画「医療情報データベースの特性と質」） (2012)
  • Author(s): 康 東天
  • Organizer: 第16回日本医療情報学会春季学術大会
  • Place of Presentation: 函館
  • Invited
• [Presentation] 日本版センチネルプロジェクトにおける標準化の課題：Jlac10（Helicsチュートリアル「医療情報を二次利用するための標準化」 (2012)
  • Author(s): 康 東天
  • Organizer: 第16回日本医療情報学会春季学術大会
  • Place of Presentation: 函館
  • Invited
• [Presentation] 臨床化学の魅力：自動化の先にあるもの（会長シンポジウム「臨床検査の再生と将来展望」） (2012)
  • Author(s): 康 東天
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 臨床検査項目標準コード（Jlac10）最新情報～今後の方向性（シンポジウム「臨床検査の医療情報」） (2012)
  • Author(s): 康 東天
  • Organizer: 第32回日本医療情報学連合大会
  • Place of Presentation: 新潟
  • Invited
• [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
  • Invited
• [Remarks] 九州大学病院検査部 臨床検査医学分野
  • URL: http://www.med.kyushu-u.ac.jp/cclm/