Phosphorylation-dependent regulation of mitochondrial functions and quality control

• Project/Area Number: 17H03676
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Rikkyo University
• Principal Investigator: OKA Toshihiko 立教大学, 理学部, 教授 (40263321)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: ミトコンドリア / ミトコンドリア品質管理 / リン酸化修飾 / リン酸化 / 品質管理

Outline of Final Research Achievements

Mitochondria with low membrane potential are eliminated by autophagy, which is called mitochondrial quality control. It is still unclear how the mitochondrial quality control is regulated by cellular signals.
We have focused on PKA-dependent phosphorylation and determined that intracellular localization of the PKA catalytic subunit isoforms. Furthermore, we found a role of the enzyme in the glycolytic pathway in mitochondrial quality control.

Academic Significance and Societal Importance of the Research Achievements

本研究では，細胞がミトコンドリア機能を制御する方法としての翻訳後修飾に着目して，ミトコンドリア機能の調節機構を明らかにしようとする点が特徴であり，ミトコンドリア表面だけでなく，これまで手付かずだったミトコンドリア内部でのリン酸化修飾を検証した点がユニークである。
本研究で得られる結果は，ミトコンドリアの機能と品質管理の理解に寄与するだけでなく，PINK1やParkinを原因遺伝子とする遺伝性パーキンソン病の発症メカニズムを理解する上でも重要な知見となる。

Research Products

• [Journal Article] The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain (2020)
  • Author(s): Nakamura S, Matsui A, Akabane S, Tamura Y, Hatano A, Miyano Y, Omote H, Kajikawa M, Maenaka K, Moriyama Y, Endo T, and Oka T
  • Journal Title: Communications biology Volume: 3 Pages: 99-99
  • DOI: 10.1038/s42003-020-0832-5
  • Peer Reviewed / Open Access
• [Journal Article] In vitro synthesis of the human calcium transporter Letm1 within cell-sized liposomes and investigation of its lipid dependency (2019)
  • Author(s): Okamura Kosuke、Matsushita Shuhei、Kato Yasuhiko、Watanabe Hajime、Matsui Aiko、Oka Toshihiko、Matsuura Tomoaki
  • Journal Title: Journal of Bioscience and Bioengineering Volume: 127 Issue: 5 Pages: 544-548
  • DOI: 10.1016/j.jbiosc.2018.11.003
  • NAID: 40021891579
  • ISSN: 1389-1723
  • Peer Reviewed / Open Access
• [Journal Article] Concentration of mitochondrial DNA mutations by cytoplasmic transfer from platelets to cultured mouse cells. (2019)
  • Author(s): Ishikawa K, Kobayashi K, Yamada A, Umehara M, Oka T, Nakada K.
  • Journal Title: PLOS ONE Volume: 14 Pages: 0213283-0213283
  • DOI: 10.1371/journal.pone.0213283
  • NAID: 120007133505
  • Peer Reviewed / Open Access
• [Journal Article] Structural insights into ubiquitin phosphorylation by PINKI. (2018)
  • Author(s): Okatsu, K., Sato, Y., Yamano, K., Matsuda, N., Negishi, L., Takahashi, A., Yamagata, A., Goto-Ito, S., Mishima, M., Ito, Y., Oka, T., Tanaka, K., and Fukai, S.
  • Journal Title: Sci. Rep. Volume: 8 Pages: 10382-10382
  • DOI: 10.1038/s41598-018-28656-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inactivation of cardiolipin synthase triggers changes in mitochondrial morphology. (2018)
  • Author(s): Matsumura, A., Higuchi, J., Watanabe, Y., Kato, M., Aoki, K., Akabane, S., Endo, T. and Oka, T.
  • Journal Title: FEBS Lett Volume: 592 Pages: 209-218
  • DOI: 10.1002/1873-3468.12948
  • Peer Reviewed / Open Access
• [Presentation] ミトコンドリア品質管理におけるTIM23複合体の新たな役割 (2019)
  • Author(s): 渡邊聖菜，岡 敏彦
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] ミトコンドリア膜透過装置コアサブユニットTIM23のミトコンドリア品質管理における役割 (2018)
  • Author(s): 渡邊聖菜，岡 敏彦
  • Organizer: 第91回日本生化学会大会
• [Presentation] ミトコンドリア品質管理におけるヘキソキナーゼの役割 (2018)
  • Author(s): 加藤雅広，三宅千絢，岡 敏彦
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] ミトコンドリア形態におけるカルジオリピンの役割 (2017)
  • Author(s): 松村綾香，樋口 准，青木啓悟，岡 敏彦
  • Organizer: 生命科学系学会合同年次大会ConBio2017