Morphological analysis of mitochondria during mitophagy

• Project/Area Number: 15K18501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Niigata University
• Principal Investigator: YAMASHITA Shunichi 新潟大学, 医歯学系, 助教 (30529095)
• Research Collaborator: JIN Xiulian ; MIHARA Katsuyoshi ; OTERA Hidenori ; YAMASHITA Tomohiro
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: マイトファジー / オートファジー / ミトコンドリア / Drp1 / ミトコンドリア分裂 / オートファゴソーム

Outline of Final Research Achievements

Mitochondria produce the vast majority of cellular energy and are essential organelles for cell survival. A damaged portion of mitochondria is degraded by autophagy (termed mitophagy) and mitophagy contributes to mitochondrial homeostasis. It has been believed so far that mitochondrial division occurs first and then the divided mitochondrial portion is recognized by autopahgy. However, morphological properties of mitochondria during mitophagy remain unclear. In the present study, I have discovered a novel division pathway of mitochondria during mitophagy. In the course of this pathway, first, mitochondrial portion of tubular mitochondria is recognized by isolation membrane. And then, the portion buds simultaneously with isolation membrane elongation. Finally, the mitochondrial portion is separated from tubular mitochondria and is completely enwrapped by autophagosome.

Research Products

• [Journal Article] Detection of Hypoxia-Induced and Iron Depletion-Induced Mitophagy in Mammalian Cells. (2017)
  • Author(s): Yamashita SI, Kanki T.
  • Journal Title: Methods Mol Biol. Volume: 印刷中 Pages: 141-149
  • DOI: 10.1007/7651_2017_19
  • ISBN: 9781493977499, 9781493977505
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] How autophagy eats large mitochondria; autophagosome formation coupled with mitochondrial fragmentation (2017)
  • Author(s): Shun-ichi Yamashita and Tomotake Kanki
  • Journal Title: Autophagy Volume: 印刷中 Issue: 5 Pages: 980-981
  • DOI: 10.1080/15548627.2017.1291113
  • Peer Reviewed
• [Journal Article] Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy. (2016)
  • Author(s): Yamashita SI, Jin X, Furukawa K, Hamasaki M, Nezu A, Otera H, Saigusa T, Yoshimori T, Sakai Y, Mihara K, Kanki T.
  • Journal Title: J Cell Biol. Volume: 215 Issue: 5 Pages: 649-665
  • DOI: 10.1083/jcb.201605093
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Constitutive activation of PINK1 leads to proteasome-mediated and non-apoptotic cell death independently of mitochondrial autophagy (2016)
  • Author(s): Akabane, S., Matsuzaki, K., Yamashita, S-I, Arai, K., Okatsu, K., Kanki, T., Matsuda, N., and Oka, T.
  • Journal Title: J. Biol. Chem. Volume: 291 Issue: 31 Pages: 16162-16174
  • DOI: 10.1074/jbc.m116.714923
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Peroxisome homeostasis: mechanisms of division and selective degradation of peroxisomes in mammals. (2016)
  • Author(s): Honsho, M., Yamashita,S., and Fujiki, Y.
  • Journal Title: Biochim. Biophys. Acta- Mol. Cell Res. Volume: 1863 Issue: 5 Pages: 984-991
  • DOI: 10.1016/j.bbamcr.2015.09.032
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mitophagy is primarily due to alternative autophagy and requires MAPK1 and MAPK14 signaling pathway. (2015)
  • Author(s): Hirota, Y.,Yamashita, S., Kurihara, Y., Jin, X., Aihara, M., Saigusa, T., Kang, D., and Kanki, T.
  • Journal Title: Autophagy Volume: 11 Issue: 2 Pages: 332-43
  • DOI: 10.1080/15548627.2015.1023047
  • Peer Reviewed / Open Access
• [Journal Article] Mitophagy in yeast: Molecular mechanisms and physiological role. (2015)
  • Author(s): Kanki T, Furukawa K, Yamashita SI.
  • Journal Title: Biochim Biophys Acta. Volume: 印刷中 Issue: 10 Pages: 2756-2765
  • DOI: 10.1016/j.bbamcr.2015.01.005
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Drp1-independet mitochondrial division occurs concurrently with autophagosome formation in mitophagy (2017)
  • Author(s): 山下俊一
  • Organizer: Joint Japan-Korea-China Young Investigator Conference (A3)
  • Place of Presentation: Seoul National University（ソウル市・韓国）
  • Year and Date: 2017-02-19
  • Int'l Joint Research / Invited
• [Presentation] マイトファジー時に見られるミトコンドリア分裂機構の解析 (2016)
  • Author(s): 山下俊一
  • 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（南魚沼群・新潟県）
  • Year and Date: 2016-11-14
• [Presentation] マイトファジー時に見られるミトコンドリア分裂機構の解析 (2016)
  • Author(s): 山下俊一
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター/東北大学川内北キャンパス（仙台市・宮城県）
  • Year and Date: 2016-09-25
• [Presentation] Drp1-independent mitochondrial division in mitophagy (2016)
  • Author(s): 山下俊一
  • Organizer: Young Investigator Conference on Autophagy (A3)
  • Place of Presentation: 新潟医療人育成センター（新潟市・新潟県）
  • Year and Date: 2016-02-18
  • Int'l Joint Research
• [Presentation] マイトファジー時に見られる特殊なミトコンドリア分裂機構 (2016)
  • Author(s): 山下俊一
  • Organizer: 第57回新潟生化学懇話会
  • Place of Presentation: 新潟医療人育成センター（新潟市・新潟県）
• [Presentation] マイトファジー時に見られるミトコンドリア形態制御機構 (2015)
  • Author(s): 山下俊一
  • Organizer: 第９回オートファジー研究会
  • Place of Presentation: 淡路夢舞台国際会議場（淡路市・兵庫県）
  • Year and Date: 2015-11-16
• [Presentation] Regulation of mitochondrial morphology Drp1-independent division in mitophagy (2015)
  • Author(s): 山下俊一
  • Organizer: Symposium on Autophagy (A3)
  • Place of Presentation: ソウル市（韓国）
  • Year and Date: 2015-10-29
  • Int'l Joint Research
• [Presentation] マイトファジーにおけるミトコンドリア形態制御因子の重要性 (2015)
  • Author(s): 山下俊一
  • Organizer: YoungMito2015
  • Place of Presentation: 一宮シーサイドオーツカ（長生郡一宮町・千葉県）
  • Year and Date: 2015-07-09
• [Presentation] マイトファジーにおけるミトコンドリア形態制御因子の重要性 (2015)
  • Author(s): 山下俊一
  • Organizer: 第６７回日本細胞生物学会大会
  • Place of Presentation: タワーホール船堀（江戸川区・東京都）
  • Year and Date: 2015-06-30
• [Remarks] 新潟大学医歯学総合研究科機能制御学分野ホームページ
  • URL: http://www.med.niigata-u.ac.jp/mit/