Comprehensive identification and function analysis of new autophagy-related genes using fly cultured cells

• Project/Area Number: 23790371
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: HIROTA Yuko 九州大学, 薬学研究科(研究院), 助教 (50588259)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: オートファジー / マイトファジー / リソソーム / ミトコンドリア

Research Abstract

Autophagy is a catabolic process that degrades cytoplasmic components and organelles, which utilizes lysosomal degradative function. We observed macroautophagy and mitophagy using a sensitive method in HeLa cells using the pH-sensitive fluorescent protein Keima. Using this method, we found that mitophagy was barely induced by carbonyl cyanide m-chlorophenylhydrazine treatment, which is widely used as an inducer of Parkin-related mitophagy, whereas a small but modest level of mitochondria was degraded by mitophagy with starvation or hypoxia. Mitophagy induced by starvation or hypoxia was not suppressed by knockdown of Atg7 and Atg12, or LC3, which are essential for conventional autophagy. Finally, we found that the MAPKs ERK2 and p38 were required for mitophagy. Based on these findings, we conclude that mitophagy in mammalian cells predominantly belongs to an alternative autophagy, and requires ERK2 and p38 signaling pathways.

Research Products

• [Journal Article] The Tor and Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32 (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., and Kanki, T.
  • Journal Title: J. Cell Sci Volume: (In Press)
  • Peer Reviewed
• [Journal Article] The Tor and Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32 (2014)
  • Author(s): Masamune Aihara, Xiulian Jin, Yusuke Kurihara, Yutaka Yoshida, Yuichi Matsushima, Masahide Oku, Yuko Hirota, Tetsu Saigusa, Yoshimasa Aoki, Takeshi Uchiumi, Tadashi Yamamoto, Yasuyoshi Sakai, Dongchon Kang, and Tomotake Kanki
  • Journal Title: Journal of Cell Science Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Casein kinase 2 is essential for mitophagy. (2013)
  • Author(s): Kanki T., Kurihara Y., Jin X., Goda T., Ono Y., Aihara M., Hirota Y., Saigusa T., Aoki Y., Uchiumi T., Kang D.
  • Journal Title: EMBO reports Volume: 14巻 Issue: 9 Pages: 788-794
  • DOI: 10.1038/embor.2013.114
  • Peer Reviewed
• [Journal Article] The physiological role of mitophagy: new insights into phosphorylation events. (2012)
  • Author(s): Hirota, Y., Kang, D., Kanki, T.
  • Journal Title: International journal of cell biology Volume: 2012 Pages: 354914-354914
  • DOI: 10.1155/2012/354914
  • Peer Reviewed
• [Journal Article] Mitophagy plays an essential role in reducing mitochondrial production of reactive oxygen species and mutation of mitochondrial DNA by maintaining mitochondrial quantity and quality in yeast (2012)
  • Author(s): Kurihara Y, Kanki T, Aoki Y, Hirota Y, Saigusa T, Uchiumi T, Kang D
  • Journal Title: J Biol Chem Volume: 287 Issue: 5 Pages: 3265-3272
  • DOI: 10.1074/jbc.m111.280156
  • Peer Reviewed
• [Journal Article] Phosphorylation of Serine 114 on Atg32 mediates mitophagy (2011)
  • Author(s): Aoki, Y., Kanki, T., Hirota, Y., Kurihara, Y., Saigusa, T., Uchiumi, T., Kang, D.
  • Journal Title: Mol Biol Cell Volume: 22 Issue: 17 Pages: 3206-3217
  • DOI: 10.1091/mbc.e11-02-0145
  • Peer Reviewed
• [Presentation] ミトコンドリア分解シグナルの解明生体機能と創薬 (2013)
  • Author(s): 廣田有子、栗原悠介、金秀蓮、三枝徹、藤本景子、田中嘉孝、神吉智丈
  • Organizer: シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2013-08-29
• [Presentation] ミトコンドリア分解シグナルの解明 (2013)
  • Author(s): 廣田有子、栗原悠介、金秀蓮、三枝徹、藤本景子、田中嘉孝、神吉智丈
  • Organizer: 生体機能と創薬シンポジウム
  • Place of Presentation: 福岡
• [Presentation] The participation of mitophagy -related genes to phosphorylation events of Atg32 (2012)
  • Author(s): 金秀蓮、神吉智丈、相原正宗、栗原悠介、廣田有子、三枝徹、康東天
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-11
• [Presentation] The participation of mitophagy-related genes to phosphorylation events of Atg32 (2012)
  • Author(s): Jin X.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] 出芽酵母に置けるマイトファジーの生理的役割 (2011)
  • Author(s): 栗原悠介、神吉智丈、廣田有子、青木義政、三枝徹、内海健、康東天
  • Organizer: 第44回酵母遺伝学フォーラム
  • Place of Presentation: 福岡
  • Year and Date: 2011-09-05
• [Presentation] Phosphorylation of Ser114 on Atg32 mediates mitophagy (2011)
  • Author(s): Aoki, Y., Kanki, T., Hirota, Y., Kurihara, Y., Saigusa, T., and Kang, D.
  • Organizer: European Meeteing on Mitochondrial Pathology
  • Place of Presentation: Spain
  • Year and Date: 2011-06-20
• [Book] Autophagy-A Double-Edged Sword-Cell Survival or Death- Rab GTPases in Autophagy (2013)
  • Author(s): Hirota, Y., Fujimoto, K., and Tanaka, Y.
  • Total Pages: 18
  • Publisher: InTech
• [Book] Autophagy - A Double-Edged Sword - Cell Survival or Death? "Rab GTPases in Autophagy" (2013)
  • Author(s): Yuko Hirota, Fujimoto Keiko, Yoshitaka Tanaka
  • Total Pages: 18
  • Publisher: InTech
• [Book] Autophagy (2013)
  • Author(s): Hirota Y.
  • Publisher: InTech
• [Remarks]
  • URL: http://mitophagy.web.fc2.com/
• [Remarks] 新潟大学バイオシグナリング研究室
  • URL: http://mitophagy.web.fc2.com/