The role of a membrane-bound glutathione transferase in the oxidative stress-induced mitochondria dysfunction

• Project/Area Number: 24790533
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: University of the Ryukyus
• Principal Investigator: IMAIZUMI Naoki 琉球大学, 医学部, 助教 (10547384)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: グルタチオントランスフェラーゼ / ミトコンドリア / 透過性遷移 / 酸化ストレス / グルタチオンとランスフェラーゼ / 肝障害 / ミトコンドリア透過性遷移 / 膜透過性遷移

Outline of Final Research Achievements

In the present study, we aimed to confirm the role of mtMGST1 in the oxidative stress-induced mitochondrial permeability transition (MPT) pore opening. We found that the inner membrane mtMGST1 and MPT regulator proteins such as ANT and CypD are involved in the oxidant peroxynitrite (PON)-induced MPT pore opening, which is mediated by a disulfide bond, and that PON induces mitochondrial swelling accompanied by formation of high molecular weight proteins complex (MPC) of mtMGST1, ANT, and CypD via caldiolipin(CL), which is a phospholipid exclusively located in mitochondria.

Research Products

• [Journal Article] Mechanisms of cell death pathway activation following drug-induced inhibition of mitochondrial complex I. (2015)
  • Author(s): Imaizumi N, Kwang Lee K, Zhang C, Boelsterli UA.
  • Journal Title: Redox Biol. Volume: 4 Pages: 279-288
  • DOI: 10.1016/j.redox.2015.01.005
  • Peer Reviewed / Open Access
• [Journal Article] Targeting mitochondria with methylene blue protects mice against acetaminophen-induced liver injury. (2015)
  • Author(s): Lee KK, Imaizumi N, Chamberland SR, Alder NN, Boelsterli UA.
  • Journal Title: Hepatology. Volume: 61(1) Issue: 1 Pages: 326-336
  • DOI: 10.1002/hep.27385
  • Peer Reviewed
• [Presentation] 酸化ストレス性ミトコンドリア機能障害に対する ジメルミ酸の影響 (2015)
  • Author(s): 今泉直樹
  • Organizer: 第42回日本毒性学会学術年会
  • Place of Presentation: 石川県立音楽堂、金沢市アートホール、ホテル日航金沢（石川県、金沢市）
  • Year and Date: 2015-06-30
• [Presentation] ジメルミ酸のミトコンドリア酸化ストレスに対する影響 Effect of the natural antioxidant, dimerumic acid on mitochondrial oxidative stress (2013)
  • Author(s): 今泉直樹
  • Organizer: 第４０回日本毒性学会
  • Place of Presentation: 千葉
• [Presentation] Formation of disulfide-linked high molecular protein complex by glutathione transferase in the mitochondrial inner membrane and adenine nucleotide translocator through peroxynitrite (2012)
  • Author(s): 今泉 直樹
  • Organizer: 第6回 アジア毒性学会学術集会
  • Place of Presentation: 仙台