Why does glycolysis take place in peroxisomes in trypanosomes?

• Project/Area Number: 25670205
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Juntendo University
• Principal Investigator: Nara Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (40276473)
• Co-Investigator(Kenkyū-buntansha): MORALES Jorge 順天堂大学, 医学部, 助教 (20596126)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: トリパノソーマ / 解糖系 / ペルオキシソーム / オルガネラ進化 / ディプロネマ / 代謝経路

Outline of Final Research Achievements

The remodelling of organelle function is increasingly appreciated as a central driver of eukaryotic biodiversity and evolution. Kinetoplastids including Trypanosoma and Leishmania have evolved specialised peroxisomes, called glycosomes. Glycosomes uniquely contain a glycolytic pathway as well as other enzymes, which underpin the physiological flexibility of these major human pathogens. The sister group of kinetoplastids are the diplonemids, which are among the most abundant eukaryotes in marine plankton. Here we demonstrate the compartmentalisation of gluconeogenesis, or glycolysis in reverse, in the peroxisomes of the free-living marine diplonemid, Diplonema papillatum. Our results suggest that peroxisome modification was already underway in the common ancestor of kinetoplastids and diplonemids, and raise the possibility that the central importance of gluconeogenesis to carbon metabolism in the heterotrophic free-living ancestor may have been an important selective driver.

Research Products

• [Journal Article] Morpholino antisense oligo inhibits trans-splicing of pre-inositol 1,4,5-trisphosphate receptor mRNA of Trypanosoma cruzi and suppresses parasite growth and infectivity. (2016)
  • Author(s): Hashimoto M, Nara T, Mita T, Mikoshiba K.
  • Journal Title: Parasitol Int. Volume: 65 Issue: 3 Pages: 175-179
  • DOI: 10.1016/j.parint.2015.12.001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells. (2016)
  • Author(s): Kobayashi I, Takahashi F, Nurwidya F, Nara T, Hashimoto M, Murakami A,
  • Journal Title: Biochem Biophys Res Commun Volume: in press Issue: 1 Pages: 125-132
  • DOI: 10.1016/j.bbrc.2016.03.064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] トリコモナス症、ジアルジア症．性感染症の全てー病原体、診断、治療、予防． (2016)
  • Author(s): 奈良武司
  • Journal Title: 臨床と微生物 Volume: 43 Pages: 157-161
• [Journal Article] A dominant negative form of inositol 1,4,5-trisphosphate receptor induces metacyclogenesis and increases mitochondrial density in Trypanosoma cruzi. (2015)
  • Author(s): Hashimoto M, Nara T, Enomoto M, Kurebayashi N, Yoshida M, Sakurai T, Mita T, Mikoshiba K.
  • Journal Title: Biochem Biophys Res Commun Volume: 466 Issue: 3 Pages: 475-480
  • DOI: 10.1016/j.bbrc.2015.09.053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Novel Method for Inducing Amastigote-To-Trypomastigote Transformation In Vitro in Trypanosoma cruzi Reveals the Importance of Inositol 1,4,5-Trisphosphate Receptor. (2015)
  • Author(s): Hashimoto M, Morales J, Uemura H, Mikoshiba K, Nara T.
  • Journal Title: PLoS One. Volume: 10 Issue: 8 Pages: e0135726-e0135726
  • DOI: 10.1371/journal.pone.0135726
  • NAID: 120006986870
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Current situation of Chagas disease in non-endemic countries (2015)
  • Author(s): Nara T.
  • Journal Title: Juntendo Med J Volume: 61 Pages: 389-395
  • NAID: 130005111511
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] シャーガス病．感染症最前線とグローバル・ヘルス (2015)
  • Author(s): 奈良武司
  • Journal Title: 医学のあゆみ Volume: 253 Pages: 119-123
• [Journal Article] シャーガス病：感染症最前線とグローバル・ヘルス (2015)
  • Author(s): 奈良武司．
  • Journal Title: 医学のあゆみ Volume: 253 Pages: 119-123
• [Journal Article] トリパノソーマ症：骨格筋症候群（第2版）上－その他の神経筋疾患を含めて－ (2015)
  • Author(s): 奈良武司．
  • Journal Title: 日本臨牀 Volume: 印刷中
• [Journal Article] Treatment with insulin-like growth factor 1 receptor inhibitor reverses hypoxia-induced epithelial-mesenchymal transition in non-small cell lung cancer (2014)
  • Author(s): Nurwidya F, Takahashi F, Kobayashi I, Murakami A, Kato M, Minakata K, Nara T, Hashimoto M, Yagishita S, Baskoro H, Hidayat M, Shimada N, Takahashi K.
  • Journal Title: Biochem Biophys Res Commun Volume: 455 Issue: 3-4 Pages: 332-338
  • DOI: 10.1016/j.bbrc.2014.11.014
  • Peer Reviewed
• [Journal Article] Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase (2014)
  • Author(s): Emmanuel Oluwadare Balogun, Daniel Ken Inaoka, Tomoo Shiba, Yasutoshi Kido, Chiaki Tsuge, Takeshi Nara, Takashi Aoki, Teruki Honma, Akiko Tanaka, Masayuki Inoue, Shigeru Matsuoka, Paul A.M. Michels, Kiyoshi Kita, Shigeharu Harada
  • Journal Title: Molecular Microbiology Volume: 94 Issue: 6 Pages: 1315-1329
  • DOI: 10.1111/mmi.12831
  • Peer Reviewed
• [Journal Article] Chagas disease: Clear and present danger (2014)
  • Author(s): Nara T.
  • Journal Title: Juntendo Med J Volume: 60 Pages: 362-365
• [Journal Article] Antisense oligonucleotides targeting parasite inositol 1,4,5-trisphosphate receptor inhibits mammalian host cell invasion by Trypanosoma cruzi (2014)
  • Author(s): Hashimoto M, Nara T, Hirawake H, Morales J, Enomoto M, Mikoshiba K.
  • Journal Title: Sci Rep Volume: 14(4231) Issue: 1 Pages: 4231-4231
  • DOI: 10.1038/srep04231
  • Peer Reviewed
• [Journal Article] Structure of the trypanosome cyanide-insensitive alternative oxidase (2013)
  • Author(s): Tomoo Shiba, Yasutoshi Kido, Kimitoshi Sakamoto, Daniel Ken Inaoka, Chiaki Tsuge, Ryoko Tatsumi,Gen Takahashi, Emmanuel Oluwadare Balogun, Takeshi Nara, Takashi Aoki, Teruki Honma, Akiko Tanaka, Masayuki Inoue, Shigeru Matsuoka, Hiroyuki Saimoto, Anthony L. Moore, Shigeharu Harada, Kiyoshi Kita
  • Journal Title: Proc. Nat1. Acad. Sci. USA Volume: 110 (12) Issue: 12 Pages: 4580-4585
  • DOI: 10.1073/pnas.1218386110
  • Peer Reviewed
• [Journal Article] Biochemical characterization of highly active Trypanosoma brucei gambiense glycerol kinase, a promising drug target (2013)
  • Author(s): Balogun EO, Inaoka DK, Shiba T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Harada S, Kita K
  • Journal Title: J Biochem Volume: 154(1) Issue: 1 Pages: 77-84
  • DOI: 10.1093/jb/mvt037
  • Peer Reviewed
• [Journal Article] Assessment of Cross-reactive Host-pathogen Antibodies in Patients With Different Stages of Chronic Chagas Disease (2013)
  • Author(s): Vicco MH, Ferini F, Rodeles L, Cardona P, Bontempi I, Lioi S, Beloscar J, Nara T, Marcipar I, Bottasso OA
  • Journal Title: Rev Esp Cardiol Volume: 66(10) Issue: 10 Pages: 791-796
  • DOI: 10.1016/j.recesp.2013.05.028
  • Peer Reviewed
• [Journal Article] Hypoxia increases gefitinib-resistant lung cancer stem cells through the activation of insulin-like growth factor 1 receptor (2013)
  • Author(s): Murakami A, Takahashi F, Nurwidya F, Kobayashi I, Minakata K, Hashimoto M, Nara T, Kato M, Tajima K, Shimada N, Iwakami S, Moriyama M, Moriyama H, Koizumi F, Takahashi K
  • Journal Title: PLoS One Volume: 9(1) Issue: 1 Pages: e86459-e86459
  • DOI: 10.1371/journal.pone.0086459
  • Peer Reviewed
• [Presentation] Inositol 1,4,5-trisphosphate receptor determines intracellular Ca2+ concentration in Trypanosoma cruzi throughout its life cycle (2016)
  • Author(s): 橋本宗明、戸井基道、呉林－国広なごみ、古川功治、茂木－平訳浩子、近江谷克裕、 櫻井隆、美田敏宏、御子柴克彦、奈良武司
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市
  • Year and Date: 2016-03-19
• [Presentation] クルーズトリパノソーマに「休眠現象」は存在するのか？ (2016)
  • Author(s): 奈良武司、平訳浩子、角田宗一郎、細谷英里奈、三井颯太、美田敏宏
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市
  • Year and Date: 2016-03-19
• [Presentation] Seroprevalence, environmental and behavioral risk factors of Toxocara canis infection among women in Swaziland, Southern Africa. (2016)
  • Author(s): Fan CK, Huang YH, Chou CM, Liao CW, Lee YL, Wang YC, Naito T, Tsubouchi A, Nara T.
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市
  • Year and Date: 2016-03-19
• [Presentation] キネトプラスチダ類の特異オルガネラ、グリコソームは糖新生起原である (2015)
  • Author(s): 奈良武司、Jorge Morales、橋本宗明、Tom A. Williams、平訳浩子、牧内貴志、坪内暁子、加賀直子、高ひかり、藤村務、美田敏宏、Frederic Bringaud、Juan L. Concepcion、橋本哲男、T. Martin Embley．
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Novel method for inducing trypomastigogenesis in vitro in Trypanosoma cruzi reveals the importance of IP3 receptor (2015)
  • Author(s): 橋本 宗明、ホルヘモラレス、御子柴克彦、奈良武司．
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Trypanosoma bruceiのシアン耐性末端酸化酵素阻害剤の解離定数と抗原虫効果 (2015)
  • Author(s): 稲岡ダニエル健、志波智夫、柘植千秋、趙理海、高橋元、上田慧、城戸康年、エマニュエルバログン、坂本君年、奈良武司、本間光貴、田仲昭子、井上将行、斎本博之、アンソニームーア、原田繁春、北潔．
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] Seroprevalence, seroconversion, and toxoplasmosis risk factors among pregnant women in Taipei City, Taiwan (2015)
  • Author(s): Chia-Kwung Fan、Ching-Sheng Hung、Hung-Wen Su、Yu-Luen Lee、Hui-Wen Weng、Yin-Chin Wang、Toshio Naito、Akiko Tsubouchi、Takeshi Nara、Giueng-Chueng Wang.
  • Organizer: 第84回日本寄生虫学会大会
  • Place of Presentation: 杏林大学、東京
  • Year and Date: 2015-03-21 – 2015-03-22
• [Book] シャーガス病（アメリカトリパノソーマ症）．人獣共通感染症改訂3版．木村哲、喜田宏編 (2015)
  • Author(s): 奈良武司
  • Total Pages: 550
  • Publisher: 医薬ジャーナル社
• [Book] トリパノソーマ症．別冊骨格筋症候群第2版上巻 (2015)
  • Author(s): 奈良武司
  • Total Pages: 471
  • Publisher: 日本臨牀社
• [Book] シャーガス病（アメリカトリパノソーマ症）：人獣共通感染症 改訂3版 (2015)
  • Author(s): 奈良武司．
  • Publisher: 医薬ジャーナル
• [Book] 寄生虫検査：臨床微生物検査ハンドブック (2015)
  • Author(s): 奈良武司
  • Publisher: 三輪書店
• [Patent(Industrial Property Rights)] トリパノソーマ関連疾患の治療薬、トリパノソーマ原虫の殺虫方法、およびその応用 (2013)
  • Inventor(s): 奈良武司、橋本宗明、御子柴克彦
  • Industrial Property Rights Holder: 奈良武司、橋本宗明、御子柴克彦
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-211448
  • Filing Date: 2013-10-08