Probes for organelle-specific autophagy

• Project/Area Number: 15K12749
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry
• Research Institution: Juntendo University
• Principal Investigator: Isei Tanida 順天堂大学, 医学部, 先任准教授 (30296868)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: オートファジー / 神経変性疾患 / パーキンソン病 / 酸化ストレス / ミトコンドリア / ペルオキシソーム / 脂肪滴 / オルガネラ / マイトファジー / リポファジー / 蛍光タンパク質 / ペキソファジー / タンパク質分解 / pHluorin / リソソーム / GFP / オルガネラ分解 / タンパク分解 / pH感受性

Outline of Final Research Achievements

Autophagy has significant roles against many diseases including neurodegenerative diseases, cardiomyopathy, type II diabetes, fatty liver, liver cancer, heart failure, and infectious diseases. Recently, organelle-specific autophagy is focused, because of the relation between autophagy and these diseases. Therefore, probes to monitor organelle-specific autophagy are awaited. We generated probes for mitochondria-specific autophagy (mitophagy) and peroxisome-specific autophagy (pexophagy).

Academic Significance and Societal Importance of the Research Achievements

今回開発した、ミトコンドリア特異的オートファジー（マイトファジー）プローブおよびペルオキシソーム特異的オートファジー（ペキソファジー）プローブにより、それぞれのオルガネラ特異的オートファジーが神経変性、老化、酸化ストレスを伴う環境因子などにより、どのように変化していくかが解析できるようになり、将来的にはこれらを抑制する創薬開発へと展開できるであろう。

Research Products

• [Journal Article] Lack of Cathepsin D in the Renal Proximal Tubular Cells Resulted in Increased Sensitivity against Renal Ischemia/Reperfusion Injury (2019)
  • Author(s): Suzuki Chigure、Tanida Isei、Ohmuraya Masaki、Oliva Trejo Juan、Kakuta Soichiro、Sunabori Takehiko、Uchiyama Yasuo
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 7 Pages: 1711-1711
  • DOI: 10.3390/ijms20071711
  • Peer Reviewed / Open Access
• [Journal Article] Blocking LC3 lipidation and ATG12 conjugation reactions by ATG7 mutant protein containing C572S (2019)
  • Author(s): Nitta A, Hori K, Tanida I, Igarashi A, Deyama Y, Ueno T, Kominami E, Sugai M, Aoki K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 508(2) Issue: 2 Pages: 521-526
  • DOI: 10.1016/j.bbrc.2018.11.158
  • Peer Reviewed
• [Journal Article] Optimization of mNeonGreen for Homo sapiens increases its fluorescent intensity in mammalian cells (2018)
  • Author(s): Tanida-Miyake Emiko、Koike Masato、Uchiyama Yasuo、Tanida Isei
  • Journal Title: PLOS ONE Volume: 13 Issue: 1 Pages: e0191108-e0191108
  • DOI: 10.1371/journal.pone.0191108
  • Peer Reviewed / Open Access
• [Journal Article] Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination (2018)
  • Author(s): Ogawa M, Matsuda R, Takada N, Tomokiyo M, Yamamoto S, Shizukusihi S, Yamaji T, Yoshikawa Y, Yoshida M, Tanida I, Koike M, Murai M, Morita H, Takeyama H, Ryo A, Guan JL, Yamamoto M, Inoue JI, Yanagawa T, Fukuda M, Kawabe H, Ohnishi M
  • Journal Title: Cellular Microbiology Volume: e12846 Issue: 8
  • DOI: 10.1111/cmi.12846
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Atg9a deficiency causes axon-specific lesions including neuronal circuit dysgenesis. (2017)
  • Author(s): Yamaguchi J, Suzuki C, Nanao T, Kakuta S, Ozawa K, Tanida I, Saitoh T, Sunabori T, Komatsu M, Tanaka K, Aoki S, Sakimura K, Uchiyama Y.
  • Journal Title: Autophagy Volume: 17 Issue: 5 Pages: 1-14
  • DOI: 10.1080/15548627.2017.1314897
  • NAID: 120006881392
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Use of pHlurorin-mKate2-human LC3 to Monitor Autophagic Responses (2017)
  • Author(s): Isei Tanida, Takashi Ueno, Yasuo Uchiyama
  • Journal Title: Methods in Enzymology Volume: 587 Pages: 87-96
  • DOI: 10.1016/bs.mie.2016.09.054
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection (2016)
  • Author(s): Yoshitaka Shirasago, Yoshimi Shimizu, Isei Tanida, Tetsuro Suzuki, Ryosuke Suzuki, Kazuo Sugiyama, Takaji Wakita, Kentaro Hanada, Kiyohito Yagi, Masuo Kondoh, and Masayoshi Fukasawa
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 5 Pages: 839-848
  • DOI: 10.1248/bpb.b15-01023
  • NAID: 130005149248
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2016)
  • Author(s): Klionsky DJ., Abdelmohsen K., Abe A., Abedin MJ.,Inomata M., et al.
  • Journal Title: Autophagy Volume: 12(1) Issue: 1 Pages: 1-222
  • DOI: 10.1080/15548627.2015.1100356
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection. (2016)
  • Author(s): Shirasago Y, Shimizu Y, Tanida I, Suzuki T, Suzuki R, Sugiyama K, Wakita T, Hanada K, Yagi K, Kondoh M, Fukasawa M.
  • Journal Title: Biol Pharm Bull. Volume: in press
  • NAID: 130005149248
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Macroautophagy is essential for killing of intracellular Burkholderia pseudomallei in human neutrophils. (2015)
  • Author(s): Rinchai D, Riyapa D, Buddhisa S, Utispan K, Titball RW, Stevens MP, Stevens JM, Ogawa M, Tanida I, Koike M, Uchiyama Y, Ato M, Lertmemongkolchai G.
  • Journal Title: Autophagy Volume: 11 Issue: 5 Pages: 748-755
  • DOI: 10.1080/15548627.2015.1040969
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] C型肝炎とオートファジー (2015)
  • Author(s): 谷田以誠
  • Journal Title: J. Gastrointest. Research Volume: 23 Pages: 205-211
• [Presentation] pHluorinを用いたオートファジー評価法 (2018)
  • Author(s): 谷田 以誠
  • Organizer: 第123回日本解剖学会総会・全国学術集会
  • Invited
• [Presentation] 酸性pH感受性緑色蛍光タンパク質pHluorinを用いたマイトファジーモニタープローブの作成 (2017)
  • Author(s): 谷田 以誠
  • Organizer: 第122回 日本解剖学会学術集会・総会
  • Place of Presentation: 長崎大学坂本キャンパス
  • Year and Date: 2017-03-28
• [Presentation] ペキソファジー高感度可視化方法の分子基盤の確立 (2017)
  • Author(s): 谷田 以誠、上野 隆、小池 正人
  • Organizer: ConBio2017 (2017年度生命科学系学会合同年次大会)
• [Presentation] 類鼻疽菌に感染した好中球で誘導されるオートファジー関連構造体についての解析 (2016)
  • Author(s): 谷田 以誠、Darawan Rinchai、小川道永、小池 正人、内山 安男、Ganjana Lertmemongkolchai、阿戸 学
  • Organizer: 第121回日本解剖学会総会
  • Place of Presentation: ぱれっと福島、郡山市、福島
  • Year and Date: 2016-03-28
• [Remarks] Google Scholar: Isei Tanida
  • URL: https://scholar.google.co.jp/citations?user=C9H0DzcAAAAJ&hl=ja&oi=ao
• [Remarks] Isei Tanida - Google Scholar
  • URL: https://scholar.google.co.jp/citations?user=C9H0DzcAAAAJ&hl=en
• [Remarks] 谷田以誠 J-GLOBAL
  • URL: http://jglobal.jst.go.jp/public/200901034804710043
• [Remarks] 順天堂大学大学院医学研究科 神経機能構造学講座
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/shinkei_kozo/k4.html
• [Remarks] Google Scholar: Isei Tanida
  • URL: https://scholar.google.co.jp/citations?user=C9H0DzcAAAAJ&hl=ja