Mitochondrial function regulated by the endoplasmic reticulum membrane protein BAP31 is associated with neurological disorders.

• Project/Area Number: 19K07045
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kochi University
• Principal Investigator: Namba Takushi 高知大学, 教育研究部総合科学系複合領域科学部門, 准教授 (10729859)
• Co-Investigator(Kenkyū-buntansha): 東 洋一郎 高知大学, 教育研究部医療学系基礎医学部門, 講師 (80380062)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ミトコンドリア / 小胞体 / オートファジー / オルガネラコミュニケーション / 小胞体-ミトコンドリア接触領域 / シグナル伝達

Outline of Research at the Start

本研究ではBAP31の機能を詳細に解析することで、小胞体とミトコンドリアのクロストークを介したミトコンドリアの恒常性維持機構の解明を目指す。計画している具体的な研究は ① BAP31とミトコンドリアの呼吸活性や品質管理の関連性の解析、②ミトコンドリア呼吸鎖complex I 複合体の形成におけるBAP31の役割、③小胞体ストレスがBAP31に与える影響の解析④ BAP31ノックアウトマウスの解析、の4つである。

Outline of Final Research Achievements

The endoplasmic reticulum membrane protein BAP31 interacts with the mitochondrial membrane protein Tom40 in the endoplasmic reticulum-mitochondria contact site to promote the transport of specific mitochondrial proteins into the mitochondria to maintain mitochondrial homeostasis. Furthermore, the BAP31-Tom40 complex dissociates upon stress and regulates mitochondrial activity by stopping the transport of mitochondrial proteins. This study reveals a new mechanism of mitochondrial homeostasis by the endoplasmic reticulum.

Academic Significance and Societal Importance of the Research Achievements

小胞体やミトコンドリアの正常な機能は私たちの健康を維持するために重要である。本研究により、小胞体とミトコンドリアがストレスに応答してどのように機能を超しているのか、どのように機能が破綻していくのかについてのメカニズムの一端が明らかになった。この成果をもとに新たな創薬のターゲットが見つかることが期待される。

Research Products

• [Int'l Joint Research] マサチューセッツ総合病院(米国)
• [Int'l Joint Research] マサチューセッツ総合病院(米国)
• [Journal Article] Lavencidin, a polyene macrolide antibiotic from Streptomyces lavendulae FRI-5 (2021)
  • Author(s): Yoshioka Takuya、Igarashi Yasuhiro、Namba Takushi、Ueda Shohei、Pait Ivy Grace Umadhay、Nihira Takuya、Kitani Shigeru
  • Journal Title: The Journal of Antibiotics Volume: 74 Issue: 5 Pages: 359-362
  • DOI: 10.1038/s41429-020-00404-z
  • Peer Reviewed
• [Journal Article] Kuanoniamine C stimulates bortezomib-induced cell death via suppression of glucose-regulated protein 78 in osteosarcoma (2020)
  • Author(s): Kayo Machihara , Takushi Namba
  • Journal Title: Biochem Biophys Res Commun Volume: 527 Issue: 1 Pages: 289-296
  • DOI: 10.1016/j.bbrc.2020.04.109
  • Peer Reviewed
• [Journal Article] BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites (2019)
  • Author(s): Namba Takushi
  • Journal Title: Science Advances Volume: 5 Issue: 6
  • DOI: 10.1126/sciadv.aaw1386
  • Peer Reviewed / Open Access
• [Journal Article] BAP31 Inhibits Cell Adaptation to ER Stress Conditions, Negatively Regulating Autophagy Induction by Interaction with STX17 (2019)
  • Author(s): Machihara Kayo、Namba Takushi
  • Journal Title: Cells Volume: 8 Issue: 11 Pages: 1350-1350
  • DOI: 10.3390/cells8111350
  • Peer Reviewed / Open Access
• [Journal Article] Identification of biosynthetic genes for the β-carboline alkaloid kitasetaline and production of the fluorinated derivatives by heterologous expression (2019)
  • Author(s): Ueda, S., Ikeda, H., Namba, T., Ikejiri, Y., Nishimoto, Y., Arai, M., Nihira, T., Kitani, S.,
  • Journal Title: J. Ind. Microbiol. Biotechnol. Volume: - Issue: 5 Pages: 739-750
  • DOI: 10.1007/s10295-019-02151-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Rejuvenating effect of lotus germ extract on senescent fibroblast via DAPK1-Beclin-1 pathway induced autophagy (2021)
  • Author(s): Namba, T., Machihara S., Iwahashi K
  • Organizer: 6th International Cell Senescence Association
  • Int'l Joint Research
• [Presentation] Bap31 Regulates Mitochondrial Function In ER-Mitochondria Contact Site. (2019)
  • Author(s): Takushi Namba
  • Organizer: ASCB/EMBO 2019 meeting. P539/B552. Washington, DC. December 7-11
  • Int'l Joint Research
• [Presentation] BAP31 Inhibits Cell Adaptation to ER Stress Conditions, Negatively Regulating Autophagy Induction by Interaction with STX17. (2019)
  • Author(s): Kayo Machihara, Takushi Namba
  • Organizer: ASCB/EMBO 2019 meeting. P539/B552. Washington, DC. December 7-11
  • Int'l Joint Research
• [Book] ミトコンドリアダイナミクス (2021)
  • Author(s): 石原直忠ほか 82名 難波卓司(p35-40)
  • Total Pages: 458
  • Publisher: エヌ・ティー・エス
  • ISBN: 9784860437466
• [Remarks] 難波研究室
  • URL: https://namba-t-lab.com/
• [Remarks] 高知大学 農林海洋科学部海洋資源科学科海洋生命科学コース 難波 研究室
  • URL: http://www.cc.kochi-u.ac.jp/~t-namba/
• [Patent(Industrial Property Rights)] アンチエイジング剤およびその製造方法 (2021)
  • Inventor(s): 難波卓司、町原加代
  • Industrial Property Rights Holder: 難波卓司、町原加代
  • Industrial Property Rights Type: 特許
  • Filing Date: 2021