Function of the AAA ATPase Cdc48 in mitochondrial morphology regulation

• Project/Area Number: 15K07007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kumamoto University
• Principal Investigator: Esaki Masatoshi 熊本大学, 発生医学研究所, 助教 (70437911)
• Research Collaborator: Chowdhury Abhijit 熊本大学, 発生医学研究所, 大学院生 ; Islam Tanvir Md. 熊本大学, 発生医学研究所, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ミトコンドリア / 膜融合 / タンパク質分解 / AAA ATPase / 分子シャペロン / AAAタンパク質 / p97/Cdc48 / ユビキチン / Cdc48 / p97

Outline of Final Research Achievements

Mitochondria form tubular structures during vegetative growth and undergo consecutive division and fusion. We have shown that the AAA ATPase Cdc48 is required for the fusion and for turnover of the fusion-responsible mitochondrial outer membrane protein Fzo1. In this study, we found that two Cdc48-interacting proteins, Ubp3 and Ubx2, are involved in mitochondrial fusion and Fzo1 turnover, respectively. Ubp3 facilitates degradation of Ubp12, a down-regulation factor for the fusion-responsible modification of Fzo1, thereby facilitating mitochondrial fusion. By contrast, Ubx2 facilitates Fzo1 turnover without affecting mitochondrial morphology.

Research Products

• [Journal Article] Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48 (2017)
  • Author(s): Esaki Masatoshi、Islam Md. Tanvir、Tani Naoki、Ogura Teru
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 5475-5475
  • DOI: 10.1038/s41598-017-05806-y
  • Peer Reviewed / Open Access
• [Journal Article] Cdc48 AAA ATPase Regulates Protein Dynamics and Turnover in Mitochondria (2017)
  • Author(s): Masatoshi Esaki
  • Journal Title: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume: 12 Pages: 161-173
  • DOI: 10.1016/b978-0-12-812146-7.00005-6
  • ISBN: 9780128121467
• [Journal Article] Microtubule severing by katanin p60 AAA+ ATPase requires the C-terminal acidic tails of both α- and β-tubulins and basic amino acid residues in the AAA+ ring pore. (2015)
  • Author(s): Johjima, A., Noi, K., Nishikori, S., Ogi, H., Esaki, M., and Ogura, T.
  • Journal Title: J. Biol. Chem. Volume: 印刷中 Issue: 18 Pages: 11762-11770
  • DOI: 10.1074/jbc.m114.614768
  • Peer Reviewed
• [Presentation] Roles of the Cdc48-cofactor complexes in regulation of mitochondrial morphology in yeast (2017)
  • Author(s): Abhijit Chowdhury, 小椋 光，江崎 雅俊
  • Organizer: ConBio2017
  • Int'l Joint Research
• [Presentation] AAA molecular chaperone Cdc48 functions with the 20S proteasome to maintain protein homeostasis (2017)
  • Author(s): Md. Tanvir Islam, 小椋 光，江崎 雅俊
  • Organizer: ConBio2017
  • Int'l Joint Research
• [Presentation] 多機能AAAタンパク質Cdc48はいかにして基質タンパク質に作用するのか？ (2016)
  • Author(s): 江崎雅俊，Md. Tanvir Islam，小椋光
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-01
  • Invited
• [Presentation] Cdc48 AAA ATPaseによるミトコンドリア融合反応の制御 (2015)
  • Author(s): 江崎雅俊，Abhijit Chowdhury, 小椋光
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
  • Int'l Joint Research
• [Remarks] 熊本大学発生医学研究所ニュープレス
  • URL: http://www.imeg.kumamoto-u.ac.jp/np82/