Molecular mechanism of mitochondrial autophagy

• Project/Area Number: 26291039
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Niigata University
• Principal Investigator: KANKI Tomotake 新潟大学, 医歯学系, 教授 (50398088)
• Co-Investigator(Renkei-kenkyūsha): YAMASHITA Shun-ichi 新潟大学, 医歯学総合研究科, 助教 (30529095) ; SAIGUSA Tetsu 新潟大学, 医歯学総合研究科, 研究員 (50421954)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: ミトコンドリア / オートファジー / 生体分子

Outline of Final Research Achievements

We have studied the molecular mechanism of mitochondria autophagy or mitophagy in yeast and mammalian cells. We found that two MAP kinases, Erk2 and p38, are required for mitophagy in mammalian cells. We also found that the Sin3-Rpd3 complex suppresses the expression of mitophagy essential factor Atg32 under the regulation of Tor in yeast. In addition, we found that when isolation membrane enwraps mitochondria, it contributes to divide mitochondria to the suitable size for enwrapping during mitophagy.

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] Mitophagy in Yeast: A Screen of Mitophagy-Deficient Mutants. (2017)
  • Author(s): Furukawa K, Kanki T.
  • Journal Title: Methods Mol Biol. Volume: 印刷中 Pages: 95-104
  • DOI: 10.1007/7651_2017_13
  • ISBN: 9781493977499, 9781493977505
  • Peer Reviewed / Acknowledgement Compliant
• [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] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2016)
  • Author(s): Klionsky DJ., Abdelmohsen K., Abe A., Abedin MJ.,Inomata M., et al.
  • Journal Title: Autophagy Volume: 12(1) Issue: 1 Pages: 1-222
  • DOI: 10.1080/15548627.2015.1100356
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Molecular Mechanisms and Physiological Role of Mitophagy in Yeast (2016)
  • Author(s): 古川健太郎、神吉智丈
  • Journal Title: KAGAKU TO SEIBUTSU Volume: 54 Issue: 4 Pages: 266-272
  • DOI: 10.1271/kagakutoseibutsu.54.266
  • NAID: 130005464585
  • ISSN: 0453-073X, 1883-6852
• [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
• [Journal Article] Tor and the Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32 in yeast. (2014)
  • Author(s): Aihara M, Jin X, Kurihara Y, Yoshida Y, Matsushima Y, Oku M, Hirota Y, Saigusa T, Aoki Y, Uchiumi T, Yamamoto T, Sakai Y, Kang D, Kanki T.
  • Journal Title: Journal of Cell Science Volume: 127 Pages: 3184-96
  • DOI: 10.1242/jcs.153254
  • Peer Reviewed / Open Access
• [Journal Article] Assays for autophagy II: Mitochondrial autophagy. (2014)
  • Author(s): Kanki T, Okamoto K.
  • Journal Title: Methods Mol Biol. Volume: 1163 Pages: 165-173
  • DOI: 10.1007/978-1-4939-0799-1_11
  • ISBN: 9781493907984, 9781493907991
  • Peer Reviewed
• [Presentation] Drp1-independent mitochondrial division for mitophagy occurs concurrently with autophagosome formation (2016)
  • Author(s): Tomotake Kanki
  • Organizer: The 4th Sino-Japan Symposium on Autophagy
  • Place of Presentation: 北京市(中国)
  • Int'l Joint Research / Invited
• [Presentation] Mitochondria autophagy in yeast and mammalian cells (2015)
  • Author(s): Tomotake Kanki
  • Organizer: A3 Autophagy Conference, Korea 2015
  • Place of Presentation: 韓国ソウル
  • Year and Date: 2015-10-28
  • Int'l Joint Research / Invited
• [Presentation] The signaling pathway regulating mitochondria autophagy (2015)
  • Author(s): Tomotake Kanki
  • Organizer: 2nd International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
  • Place of Presentation: 東大医科研
  • Year and Date: 2015-01-23 – 2015-01-24
  • Invited
• [Presentation] Signaling pathways regulating mitophagy in yeast (2014)
  • Author(s): Tomotake Kanki
  • Organizer: 2014 Northeastern Asian Symposium on Autophagy
  • Place of Presentation: Busan, Korea
  • Year and Date: 2014-12-18 – 2014-12-21
  • Invited
• [Remarks] 新潟大学大学院医歯学総合研究科 機能制御学分野
  • URL: http://www.med.niigata-u.ac.jp/mit/
• [Remarks] 新潟大学大学院医歯学総合研究科機能制御学分野
  • URL: http://www.med.niigata-u.ac.jp/mit/