Regulation of mitochondrial biogenesis and function by necdin-Sirt1 complex

• Project/Area Number: 25830053
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Osaka University
• Principal Investigator: Hasegawa Koichi 大阪大学, たんぱく質研究所, 助教 (20546783)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ミトコンドリア / 神経変性疾患 / PGC-1alpha / Necdin / パーキンソン病 / ニューロン / 神経保護 / ROS / 神経発生

Outline of Final Research Achievements

I examined the regulation of mitochondrial biogenesis and the mechanism of neuroprotection against mitochondrial insults by necdin and PGC-1α. Necdin suppressed PGC-1α degradation via ubiquitin-proteasome pathway to promote mitochondrial biogenesis and to protect neurons against mitochondrial insults.

Research Products

• [Int'l Joint Research] Columbia University(米国)
• [Journal Article] Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults. (2016)
  • Author(s): Hasegawa, K., Yasuda, T., Shiraishi, C., Fujiwara, K., Przedborski, S., Mochizuki, H., Yoshikawa, K.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 10943-10943
  • DOI: 10.1038/ncomms10943
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Necdin controls EGFR signaling linked to astrocyte differentiation in primary cortical progenitor cells (2016)
  • Author(s): Izumi Fujimoto, Koichi Hasegawa, Kazushiro Fujiwara, Masashi Yamada and Kazuaki Yoshikawa
  • Journal Title: Cellular Signalling Volume: 28 Pages: 94-107
  • Peer Reviewed / Open Access
• [Journal Article] Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase (2014)
  • Author(s): Gur, I., Fujiwara, K., Hasegawa, K., Yoshikawa, K.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e99503-e99503
  • DOI: 10.1371/journal.pone.0099503
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antagonistic interplay between necdin and Bmi1 controls proliferation of neural precursor cells in the embryonic mouse neocortex (2014)
  • Author(s): Minamide, R., Fujiwara, K., Hasegawa, K., Yoshikawa, K.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e84460-e84460
  • DOI: 10.1371/journal.pone.0084460
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Necdin controls proliferation and apoptosis of embryonic neural stem cells in an oxygen tension-dependent manner (2013)
  • Author(s): Huang, Z., Fujiwara, K., Minamide, R., Hasegawa, K., Yoshikawa, K.
  • Journal Title: Journal of Neuroscience Volume: 33 Issue: 25 Pages: 10362-10373
  • DOI: 10.1523/jneurosci.5682-12.2013
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Necdin promotes mitochondrial biogenesis to prevent neurodegeneration in experimental Parkinson’s disease (2015)
  • Author(s): Koichi Hasegawa, Toru Yasuda, Chinatsu Shiraishi, Kazushiro Fujiwara, Hideki Mochizuki, Kazuaki Yoshikawa
  • Organizer: Neuroscience 2015 45th Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] Necdin downregulates EGFR signaling in cortical neural precursor cells to suppress gliogenesis (2015)
  • Author(s): Izumi Fujimoto, Koichi Hasegawa, Kazushiro Fujiwara, Kazuaki Yoshikawa
  • Organizer: Neuroscience 2015 45th Annual Meeting
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Promotion of neuronal mitochondrial biogenesis by necdin: Neuroprotection in experimental Parkinsonism (Necdinによるニューロン内ミトコンドリア生合成の促進：実験的パーキンソンニズムにおける神経保護) (2015)
  • Author(s): 吉川和明、長谷川孝一、安田徹、望月秀樹
  • Organizer: 第38回日本神経科学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-29
  • Int'l Joint Research / Invited
• [Presentation] Necdin regulates RanGAP1 sumoylation during neuronal differentiation (2014)
  • Author(s): Kazushiro Fujiwara, Koichi Hasegawa, Kazuaki Yoshikawa
  • Organizer: Neuroscience 2014 44th Annual Meeting
  • Place of Presentation: Walter E. Washington Convention Center (Washington DC)
  • Year and Date: 2014-11-15
• [Presentation] Necdinによる上皮成長因子受容体シグナルの制御機構 (2014)
  • Author(s): 藤本泉、長谷川孝一、藤原一志郎、吉川和明
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会館（京都）
  • Year and Date: 2014-10-18
• [Presentation] Necdin promotes mitochondrial function in neurons: neuroprotection in Parkinson’s disease models (Necdinによるニューロン内ミトコンドリア機能の促進：パーキンソン病モデルにおける神経保護作用) (2014)
  • Author(s): 長谷川孝一、安田徹、白石千夏、藤原一志郎、望月秀樹、吉川和明
  • Organizer: 第57回日本神経化学会大会
  • Place of Presentation: 奈良県文化会館 奈良県新公会堂（奈良）
  • Year and Date: 2014-09-30
• [Presentation] Necdin suppresses PIAS1 SUMO E3 ligase activity by promoting ubiquitin-dependent degradation (2013)
  • Author(s): Ibrahim Gur, Kazushiro Fujiwara, Koichi Hasegawa, Kazuaki Yoshikawa
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] NecdinによるRanGAP1のSUMO化制御 (2013)
  • Author(s): 藤原一志郎、長谷川孝一、吉川和明
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] NecdinによるPGC-1αの安定化を介したニューロン内ミトコンドリア生合成の促進
  • Author(s): 長谷川孝一、白石千夏、藤原一志郎、吉川和明
  • Organizer: 第56回日本神経化学会大会 (Neuro2013)
  • Place of Presentation: 京都国際会館（京都）
• [Presentation] NecdinとBmi1の拮抗的相互作用による神経幹細胞の増殖制御
  • Author(s): 南出良平、長谷川孝一、藤原一志郎、吉川和明
  • Organizer: 第56回日本神経化学会大会 (Neuro2013)
  • Place of Presentation: 京都国際会館（京都）
• [Presentation] Necdinは脳室下帯における神経前駆細胞の増殖を制御する
  • Author(s): 橋長秀典、長谷川孝一、藤原一志郎、吉川和明
  • Organizer: 第56回日本神経化学会大会 (Neuro2013)
  • Place of Presentation: 京都国際会館（京都）
• [Presentation] NecdinによるPGC-1αを介したニューロン内ミトコンドリア機能の促進
  • Author(s): 長谷川孝一、白石千夏、藤原一志郎、吉川和明
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] 神経発生における哺乳類Smc5/6複合体要素の発現と安定化
  • Author(s): 片山雄太、藤原一志郎、長谷川孝一、吉川和明
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] Necdin天然変性領域の機能解析
  • Author(s): 藤本泉、長谷川孝一、藤原一志郎、吉川和明
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Remarks] Press Release: タンパク質ネクジンがミトコンドリア障害による神経細胞死を防ぐ
  • URL: http://www.protein.osaka-u.ac.jp/achievement/promotion-of-mitochondrial-biogenesis-by-necdin/
• [Remarks] 大阪大学 蛋白質研究所 神経発生制御研究室ホームページ
  • URL: http://www.protein.osaka-u.ac.jp/regulation/index_jap.html
• [Remarks] 大阪大学 蛋白質研究所 神経発生制御研究室ホームページ
  • URL: http://www.protein.osaka-u.ac.jp/regulation/index_jap.html