An analysis of the mechanism of the alternative autophagy

• Project/Area Number: 15K19004
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Honda Shinya 東京医科歯科大学, 難治疾患研究所, 助教 (90532672)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: オートファジー / 赤血球 / がん / 中心体

Outline of Final Research Achievements

Macroautophagy is a central mechanism in cellular metabolism by degrading parts of their cytoplasm and organelles using lysosomal enzymes. Previously, our group discovered the macroautophagy independent of Atg5 and Atg7, named Alternative autophagy. Recently, we reported alternative autophagy have an essential role for mitochondria clearance during erythrocyte differentiation.
This project aims to unravel the mechanisms of the alternative autophagy. To determine the essential molecule for the progression of alternative autophagy, we examine the proteome and microarray analysis using erythroid cells derived from wild type and alternative autophagy deficient mice. From these analysis, we identified the two candidate proteins, phospholipase and ubiquitin ligase. Contribution of both proteins to the alternative autophagy was determined by an analysis using MEF cells. In addition, we identified new function of conventional autophagy for the cell migration and regulation of centrosome number.

Research Products

• [Journal Article] Autophagy controls centrosome number. (2017)
  • Author(s): Honda S, Shimizu S
  • Journal Title: Oncotarget Volume: 8 Issue: 9 Pages: 14277-14278
  • DOI: 10.18632/oncotarget.15362
  • Peer Reviewed / Open Access
• [Journal Article] Autophagy controls centrosome number by degrading Cep63. (2016)
  • Author(s): Watanabe Y, Honda S, Konishi A, Satoko Arakawa S, Murohashi M, Yamaguchi H, Torii S, Tanabe M, Tanaka S, Warabi E, Shimizu S.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 13508-13508
  • DOI: 10.1038/ncomms13508
  • NAID: 120007129257
  • Peer Reviewed / Open Access
• [Journal Article] Autophagy suppresses cell migration by degrading GEF-H1, a RhoA GEF (2016)
  • Author(s): T. Yoshida, M. Tsujioka, S. Honda, S. Shimizu
  • Journal Title: Oncotarget Volume: 7 Issue: 23 Pages: 34420-9
  • DOI: 10.18632/oncotarget.8883
  • Peer Reviewed / Open Access
• [Journal Article] Identification of PPM1D as an essential Ulk1 phosphatase for genotoxic stress-induced autophagy. (2016)
  • Author(s): Torii S, Yoshida T, Arakawa S, Honda S, Nakanishi A, Shimizu S.
  • Journal Title: EMBO Rep. Volume: 17 Pages: 1552-1564
  • Peer Reviewed
• [Presentation] オートファジーによる中心体蛋白質Cep63の分解を介した中心体数の制御 (2017)
  • Author(s): 本田真也
  • Organizer: 細胞競合・ダイイングコード 若手合同会議
  • Place of Presentation: ホテルコスモスクエア国際交流センター（大阪府）
  • Year and Date: 2017-01-17
• [Presentation] オートファジーによるCep63の分解を介した中心体数の制御 (2016)
  • Author(s): 本田真也、渡辺雄一郎、小西昭充、室橋道子、荒川聡子、山口啓史、清水重臣
  • Organizer: 第39回日本分子生物学会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2016-11-30
• [Presentation] オートファジーによる中心体タンパク質Cep63の分解を介した中心体数の制御 (2016)
  • Author(s): 本田真也
  • Organizer: 第10回オートファジー研究会
  • Place of Presentation: NASPAニューオータニ（新潟県）
  • Year and Date: 2016-11-14
• [Presentation] 赤血球成熟段階のミトコンドリア除去における新規オートファジーの役割 (2016)
  • Author(s): 本田真也
  • Organizer: 酸素生物学・ダイイングコード合同若手会議
  • Place of Presentation: 一の宮シーサイドオーツカ (千葉県)
  • Year and Date: 2016-01-26
• [Presentation] 赤血球成熟段階のミトコンドリア除去における新規オートファジーの役割 (2015)
  • Author(s): 本田真也
  • Organizer: 第９回オートファジー研究会・第３回新学術「オートファジー」班会議
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路島）
  • Year and Date: 2015-11-15