Functional analysis of AAA ATPase Cdc48p on regulation of mitochondrial morphology

• Project/Area Number: 24770189
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Kumamoto University
• Principal Investigator: ESAKI Masatoshi 熊本大学, 発生医学研究所, 助教 (70437911)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: AAAシャペロン / ミトコンドリア / ATPase / Cdc48 / 融合 / AAA ATPase / 膜融合 / Cdc48p / p97

Research Abstract

Mitochondria undergo continuous fusion and fission, which maintain dynamic tubular morphology. We have shown that loss-of-function mutations of Cdc48p, a cytosolic AAA chaperone, induce mitochondrial aggregation. Further analyses revealed that mitochondrial fusion seems to be perturbed in Cdc48p mutants. Moreover, we explored partner proteins functioning together with Cdc48p in mitochondrial morphology regulation, and found that deletion of Shp1p induces aberrant mitochondrial morphology. These results suggests that the Cdc48p-Shp1p complex regulates the mitochondrial fusion event.

Research Products

• [Journal Article] A conserved a helix of Bcs1, a mitochondrial AAA chaperone, is required for the Respiratory Complex III maturation (2014)
  • Author(s): Rie Sawamura, Teru Ogura and Masatoshi Esaki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 443 Issue: 3 Pages: 997-1002
  • DOI: 10.1016/j.bbrc.2013.12.084
  • Peer Reviewed
• [Journal Article] Sec16 influences transitional ER sites by regulating rather than organizing COPII (2013)
  • Author(s): Nike Bharucha, Yang Liu, Effrosyni Papanikou, Conor McMahon, Masatoshi Esaki, Philip D. Jeffrey, Frederick M. Hughson, and Benjamin S. Glick
  • Journal Title: Mol. Biol. Cell Volume: 24 Issue: 21 Pages: 3406-3419
  • DOI: 10.1091/mbc.e13-04-0185
  • Peer Reviewed
• [Journal Article] The Tom40 assembly process probed using the attachment of different intra-mitochondrial sorting signals (2012)
  • Author(s): T. Shiota, M. Maruyama, M. Miura, Y. Tamura, K. Yamano, M. Esaki, and T. Endo
  • Journal Title: Mol. Biol. Cell Volume: 23 Issue: 20 Pages: 3936-3947
  • DOI: 10.1091/mbc.e12-03-0202
  • Peer Reviewed
• [Journal Article] Cdc48p/p97-mediated regulation of mitochondrial morphology is Vms1p independent. (2012)
  • Author(s): Esaki, M., and Ogura, T.
  • Journal Title: J. Struct. Biol. Volume: (in press) Issue: 2 Pages: 112-120
  • DOI: 10.1016/j.jsb.2012.04.017
  • Peer Reviewed
• [Journal Article] Caenorhabditis elegans fidgetin homolog FIGL-1, a nuclear-localized AAA ATPase, binds to SUMO. (2012)
  • Author(s): Onitake, A., Yamanaka, K., Esaki, M., and Ogura, T.
  • Journal Title: J. Struct. Biol. Volume: (in press) Issue: 2 Pages: 143-151
  • DOI: 10.1016/j.jsb.2012.04.022
  • Peer Reviewed
• [Journal Article] The C-terminal -helix of SPAS-1, a Caenorhabditis elegans spastin homologue, is crucial for microtubule severing. (2012)
  • Author(s): Onitake, A., Matsushita-Ishiodori, Y., Johjima, A., Esaki, M., Ogura, T., and Yamanaka, K.
  • Journal Title: J. Struct. Biol. Volume: (in press) Issue: 2 Pages: 138-142
  • DOI: 10.1016/j.jsb.2012.04.010
  • Peer Reviewed
• [Presentation] Yeast Cdc48-20S proteasome complex in vitro and in vivo (2014)
  • Author(s): Masatoshi Esaki, Kentaro Noi, and Teru Ogura
  • Organizer: 231st IMEG seminars & Minisymposium
  • Place of Presentation: 熊本大学発生医学研究所(熊本市)
• [Presentation] In vivoにおいてCdc48は20Sプロテアソーム複合体と相互作用する (2013)
  • Author(s): 江崎雅俊,野井健太郎,佐伯泰,小椋光
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際展示場(神戸市)
• [Presentation] 呼吸鎖複合体III形成におけるAAA分子シャペロンBcs1pのN末端の機能解析 (2013)
  • Author(s): 澤村理英,江崎雅俊,小椋光
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸国際展示場(神戸市)
• [Presentation] Dynamics of p97 and the 26S proteasome in action revealed by high-speed atomic force microscopy (2013)
  • Author(s): Teru Ogura, Kentaro Noi, Takashi Okuno, Ken-ichi Arita-Morioka, Daisuke Yamamoto, Akiko Okawa, Hikaru Tsuchiya, Yasushi Saeki, Toshio Ando, Masatoshi Esaki, and Kunitoshi Yamanaka
  • Organizer: EMBO Workshop on AAA+ Proteins : from mechanism and disease to targets
  • Place of Presentation: Commundo Hotel Neuss (Neuss, Germany)
• [Presentation] Non-conservation of the aromatic residue in the D1 pore loop of yeast Cdc48 is essential for cell viability (2013)
  • Author(s): Masatoshi Esaki and Teru Ogura
  • Organizer: EMBO Workshop on AAA+ Proteins : from mechanism and disease to targets
  • Place of Presentation: Commundo Hotel Neuss (Neuss, Germany)
• [Presentation] The N-terminal region of Bcs1p is important for the respiratory chain complex III assembly (2013)
  • Author(s): Rie Sawamura, Masatoshi Esaki, and Teru Ogura
  • Organizer: EMBO Workshop on AAA+ Proteins : from mechanism and disease to targets
  • Place of Presentation: Commundo Hotel Neuss (Neuss, Germany)
• [Presentation] AAA chaperones, focusing on the molecular mecanism of p97 (2013)
  • Author(s): Teru Ogura, Kentaro Noi, Ken-ichiArita-Morioka, Daisuke Yamamoto, Toshio Ando, Shingo Nishikori, Masatoshi Esaki, and Kunitoshi Yamanaka
  • Organizer: EMBO Conference The biology of molecular chaperones : From molecules, organelles and cells to misfolding diseases
  • Place of Presentation: Hotel Flamingo Resort (Santa Margherita di Pula, Italy)
• [Presentation] Non-conservation of the aromatic residue in the D1 pore loop of yeast Cdc48 is essential for cell viability (2013)
  • Author(s): Masatoshi Esaki, Teru Ogura
  • Organizer: EMBO Workshop on AAA+ proteins: From mechanisms and disease to targets
  • Place of Presentation: Neuss, Germany
• [Presentation] In vivoにおいてCdc48は20Sプロテアソーム複合体と相互作用する (2013)
  • Author(s): 江崎雅俊，野井健太郎，佐伯泰，小椋光
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] 呼吸鎖複合体III形成におけるAAA分子シャペロンBcs1pのN末端の機能解析 (2013)
  • Author(s): 澤村理英，江崎雅俊，小椋光
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸