Clarification of the molecular mechanism and development of novel nutritional therapy of reticular dysgenesis as mitochondrial disease

• Project/Area Number: 25750042
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: The University of Tokushima
• Principal Investigator: TANIMURA Ayako 徳島大学, 大学院医歯薬学研究部, 助教 (10610199)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: AK2 / ATP / ROS / UPR / 好中球 / 細胞分化 / 細網異形成症 / ミトコンドリア / アデニンヌクレオチド代謝 / 血球系分化 / 小胞体ストレス / CKMT / T細胞

Outline of Final Research Achievements

Adenylate kinase 2 (AK2) is an energy-metabolic enzyme in mitochondrial intermembrane space. We studied about the mechanism of neutrophil differentiation arrest by AK2 deficiency in reticular dysgenesis. By analyzing macrophage and neutrophil differentiation using HL-60 cell line, we found that AK2 is essential for neutrophil differentiation and AK2 knockdown caused increased ROS production. Additionally, differentiation- and stage-specific activation of unfolded protein response (UPR) was observed during macrophage and neutrophil differentiation. We found that differentiation-specific UPR may be required for each differentiation. These results provided important hints to develop a new therapy for reticular dysgenesis.

Research Products

• [Journal Article] Differential expression of adenine nucleotide converting enzymes in mitochondrial intermembrane space: a potential role of adenylate kinase isozyme 2 in neutrophil differentiation. (2014)
  • Author(s): Ayako Tanimura, Taigo Horiguchi, Keiko Miyoshi, Hiroko Hagita, Takafumi Noma
  • Journal Title: PLoS ONE Volume: 9 Issue: 2 Pages: e89916-e89916
  • DOI: 10.1371/journal.pone.0089916
  • NAID: 120006783221
  • Peer Reviewed
• [Presentation] Adenylate Kinase 2 Regulates Neutrophil Differentiation Via Mitochondrial function. (2014)
  • Author(s): Ayako Tanimura
  • Organizer: The 3rd ASEAN Plus and Tokushima Joint International Conference
  • Place of Presentation: Imperial Aryaduta Hotel, Makassar, Indonesia
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] A role of adenine nucleotide converting enzymes in the mitochondrial intermembrane space on the hematopoietic cell differentiation
  • Author(s): Ayako Tanimura, Taigo Horiguchi, Keiko Miyoshi, Hiroko Hagita, Takafumi Noma
  • Organizer: Keystone Symposia The Chemistry and Biology of Cell Death (Q6) joint with the meeting on Mitochondrial Dynamics and Physiology (Q5)
  • Place of Presentation: Santa Fe Community Convention Center, Santa Fe, New Mexico, USA
• [Presentation] アデニル酸キナーゼ２の血球系分化への影響
  • Author(s): 谷村 綾子、堀口 大吾、萩田 浩子、三好 圭子、野間 隆文
  • Organizer: 第54回日本生化学会中国・四国支部例会
  • Place of Presentation: 徳島大学 大塚講堂、徳島市