Roles of endogenous small molecule in autophagy induction

• Project/Area Number: 25282236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Tohoku University
• Principal Investigator: ARIMOTO Hirokazu 東北大学, 生命科学研究科, 教授 (60262789)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: オートファジー / 細菌感染 / 8-ニトロcGMP / タンパク質修飾 / 細胞内情報伝達 / 活性酸素 / 医薬品探索

Outline of Final Research Achievements

Autophagy is a major intracellular degradation system that serves to maintain homeostasis and to suppress disease progression. Majority of autophagy processes are believed to be non-selective but there are some exceptions. These selective autophagy processes must have different mechanism from canonical autophagy. We have examined in this study whether endogenous small molecules are involved in the selection mechanism. Under the inflammation conditions by bacterial infection, a nitrated nucleotide: 8-nitro-cGMP forms in the host cells. I found this nucleotide accumulated around the invading bacteria cells (group A streptococcus) and this accumulation was found to be an early marker for selective autophagic degradation of the bacterial cells.

Research Products

• [Journal Article] Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria. (2013)
  • Author(s): Ito C, Saito Y, Nozawa T, Fujii S, Sawa T, Inoue H, Matsunaga T, Khan S, Akashi S, Hashimoto R, Aikawa C, Takahashi E, Sagara H, Komatsu M, Tanaka K, Akaike T, Nakagawa I, Arimoto H.
  • Journal Title: Mol. Cell Volume: 52 Issue: 6 Pages: 794-804
  • DOI: 10.1016/j.molcel.2013.10.024
  • Peer Reviewed / Open Access
• [Presentation] S-グアニル化を起点とする細胞内分解経路 (2016)
  • Author(s): 有本博一
  • Organizer: 第１１回 レドックス・ライフイノベーションシンポジウム
  • Place of Presentation: 東京都文京区
  • Year and Date: 2016-03-18
  • Invited
• [Presentation] 内因性ヌクレオチドが関与する選択的オートファジーの分子機構 (2015)
  • Author(s): 有本博一
  • Organizer: 日本農芸化学会 第150回 東北支部大会 シンポジウム
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] 細菌感染症克服にむけた化学生物学研究 (2015)
  • Author(s): 有本博一
  • Organizer: 平成27年度 化学系学協会 東北大会 有機化学コロキウム
  • Place of Presentation: 青森県弘前市
  • Year and Date: 2015-09-13
  • Invited
• [Presentation] 内因性低分子による選択的オートファジーの制御機構 (2015)
  • Author(s): 有本博一
  • Organizer: 第50回 天然物談話会
  • Place of Presentation: 宮城県岩沼市
  • Year and Date: 2015-07-03
  • Invited
• [Presentation] Roles of 8-nitro-cGMP in autophagy regulation (2015)
  • Author(s): Hirokazu Arimoto
  • Organizer: The 7th International conference on cGMP
  • Place of Presentation: Trier, Gernany
  • Year and Date: 2015-06-19
  • Int'l Joint Research / Invited
• [Presentation] 細菌感染証克服にむけた化学生物学研究 (2015)
  • Author(s): 有本博一
  • Organizer: 日本化学会 第95春季年会
  • Place of Presentation: 日本大学理工学部船橋キャンパス／薬学部
  • Year and Date: 2015-03-26
  • Invited
• [Presentation] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria (2014)
  • Author(s): Hirokazu Arimoto
  • Organizer: The 4th Joint Campus Asia symposium
  • Place of Presentation: 東北大学，仙台市
  • Year and Date: 2014-11-27
  • Invited
• [Presentation] 内因性ニトロ化ヌクレオチドがオートファジー制御に果たす役割 (2014)
  • Author(s): 有本博一
  • Organizer: 第87回 日本生化学会大会 シンポジウム：新しい側面を見せるオートファジー：その高次機能に迫る
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-16
  • Invited
• [Presentation] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria (2014)
  • Author(s): Hirokazu Arimoto
  • Organizer: The 13th Awaji International Forum on Infection and Immunity in Nara
  • Place of Presentation: 奈良県新公会堂，奈良市
  • Year and Date: 2014-09-23
  • Invited
• [Presentation] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria (2014)
  • Author(s): Hirokazu Arimoto
  • Organizer: Nitric Oxide-Nitrite/Nitrate Conference
  • Place of Presentation: Renaissance Cleveland Hotel, Cleveland, Ohio, USA
  • Year and Date: 2014-06-18
  • Invited
• [Presentation] ニトロ化ヌクレオチドがオートファジー誘導制御に果たす役割 (2014)
  • Author(s): 有本博一
  • Organizer: 新規素材探索研究会 第13回セミナー
  • Place of Presentation: 新横浜フジビューホテル，横浜市
  • Year and Date: 2014-06-06
  • Invited
• [Presentation] Endogenous Nitrated Nucleotide Is a Key Mediator of Autophagy and Innate Defense against Bacteria (2014)
  • Author(s): Arimoto, H.
  • Organizer: Gordon Research COnferences: Autophagy in Stress, Development & Disease
  • Place of Presentation: ルッカ市，イタリア
  • Year and Date: 2014-03-19
  • Invited
• [Book] Handbook of Experimental Pharmacology (2016)
  • Author(s): Hirokazu Arimoto, Daiki Takahashi
  • Publisher: Springer
• [Remarks] 細胞から細菌を排除するための鍵分子発見
  • URL: http://www.tohoku.ac.jp/japanese/2013/11/press20131115-01.html