Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes

• Project/Area Number: 26460274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Nara Medical University (2016); Kyoto University (2014-2015)
• Principal Investigator: Nakagawa Takahiko 奈良県立医科大学, 医学部, 研究教授 (60641595)
• Co-Investigator(Kenkyū-buntansha): 李 頴 京都大学, 医学研究科, 特定研究員 (30437222) ; 小沢 将太 京都大学, 医学研究科, 研究員 (70643568)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎臓病 / ポドサイト / ミトコンドリア / 解糖系 / 未分化ポドサイト / ATP / 足突起 / ＡＴＰ / 細胞内分布 / アクチン

Outline of Final Research Achievements

Differentiated podocytes maintain glomerular physiology and require substantial levels of energy. Mitochondria and glycolysis are two major producers of ATP, but the precise roles of each in podocytes remain unknown. Mitochondria in differentiated podocytes are present in the central part of cell body. However, blocking mitochondria had minor effects on cell shape and migratory ability. In contrast, blocking glycolysis significantly reduced the formation of lamellipodia, a cortical area of these cells, and decreased cell migratory ability. Intracellular ATP distribution in lamellipodia was regulated only by glycolysis. Inhibiting glycolysis resulted in apoptosis, prevented differentiation, and impaired lamellipodia formation while inhibition of mitochondria reduced synaptopodin expression. These data suggest that mitochondria and glycolysis play parallel but distinct roles in differentiated and differentiating podocytes.

Research Products

• [Journal Article] Glycolysis, but not Mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes (2015)
  • Author(s): Ozawa S., Ueda S., Imamura H., Mori K., Asanuma K., Yanagita M., Nakagawa T.
  • Journal Title: Scientific Rep Volume: 5 Issue: 1 Pages: 18575-18575
  • DOI: 10.1038/srep18575
  • NAID: 130007901070
  • Peer Reviewed / Open Access
• [Presentation] ポドサイト細胞cell cortex部位での細胞内ATP分布は解糖系が担う (2015)
  • Author(s): 小沢将太、上田修子、今村博臣、森 潔、浅沼克彦、柳田素子、仲川孝彦
  • Organizer: 第27回日本糖尿病性腎症研究会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-05
• [Presentation] 腎臓糸球体構成細胞ポドサイト細胞における、ATP産生に注目した解糖系とミトコンドリアの異なる役割 (2015)
  • Author(s): 小沢将太、上田修子、今村博臣、森 潔、浅沼克彦、柳田素子、仲川孝彦
  • Organizer: 第38回日本分子生物学会年回 第88回日本生化学会大会 合同大会
  • Place of Presentation: 東京
  • Year and Date: 2015-12-01
• [Presentation] ENOS and diabetic nephropathy (2015)
  • Author(s): Takahiko Nakagawa
  • Organizer: 48th Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-03
  • Int'l Joint Research / Invited
• [Presentation] Distinct Roles of Glycolysis and Mitochondria in Podocytes (2015)
  • Author(s): Shota Ozawa, Kiyoshi Mori, Katsuhiko Asanuma, Motoko Yanagita and Takahiko Nakagawa
  • Organizer: 48th Annual Meeting of American Society of Nephrology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-11-03
  • Int'l Joint Research