Regulation of glucose metabolism pathway by nucleoredoxin

• Project/Area Number: 26460364
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka University
• Principal Investigator: Funato Yosuke 大阪大学, 微生物病研究所, 助教 (60505775)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: nucleoredoxin / 代謝 / グルコース / グルコース代謝 / NRX / 活性酸素 / PFK / レドックス

Outline of Final Research Achievements

Nucleoredoxin (NRX) is a Thioredoxin family protein. We searched for novel binding protein for NRX, and identified glycolysis enzyme PFK1 as a major one.
To clarify the regulation of glycolytic pathway by NRX, we performed metabolome analyses with wild type and NRX-deficient MEF cells. We found that the metabolites produced downstream of PFK1, such as lactate, decreased, and the products of pentose phosphate pathway, which diverges at the upstream of PFK1, increased. Thus, these results strengthen the notion that NRX regulates the balance between glycolytic pathway and the pentose phosphate pathway through PFK1.

Research Products

• [Journal Article] Phosphatase of regenerating liver maintains cellular magnesium homeostasis (2018)
  • Author(s): Yoshida A, Funato Y, Miki H
  • Journal Title: Biochem J. Volume: 475 Issue: 6 Pages: 1129-1139
  • DOI: 10.1042/bcj20170756
  • Peer Reviewed
• [Journal Article] CrossTalk proposal: CNNM proteins are Na+/Mg2+exchangers playing a central role in transepithelial Mg2+(re)absorption (2018)
  • Author(s): Funato Y, Furutani K, Kurachi Y, Miki H
  • Journal Title: J Physiol. Volume: 596 Issue: 5 Pages: 743-746
  • DOI: 10.1113/jp275248
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Visualization of long-term Mg2+ dynamics in apoptotic cells using a novel targetable fluorescent probe (2017)
  • Author(s): Matsui Y, Funato Y, Imamura H, Miki H, Mizukami S, Kikuchi K
  • Journal Title: Chem Sci. Volume: 8 Issue: 12 Pages: 8255-8264
  • DOI: 10.1039/c7sc03954a
  • Peer Reviewed / Open Access
• [Journal Article] Renal function of cyclin M2 Mg2+ transporter maintains blood pressure. (2017)
  • Author(s): Funato Y, Yamazaki D, Miki H.
  • Journal Title: J Hypertens. Volume: 35 Issue: 3 Pages: 585-592
  • DOI: 10.1097/hjh.0000000000001211
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phosphocysteine in the PRL-CNNM pathway mediates magnesium homeostasis. (2016)
  • Author(s): Gulerez I, Funato Y, Wu H, Yang M, Kozlov G, Miki H, Gehring K.
  • Journal Title: EMBO Rep. Volume: 17 Pages: 1890-1900
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mg²⁺ Extrusion from Intestinal Epithelia by CNNM Proteins Is Essential for Gonadogenesis via AMPK-TORC1 Signaling in Caenorhabditis elegans (2016)
  • Author(s): Ishii T, Funato Y, Hashizume O, Yamazaki D, Hirata Y, Nishiwaki K, Kono N, Arai H, Miki H.
  • Journal Title: PLoS Genet. Volume: 12 Issue: 8 Pages: e1006276-e1006276
  • DOI: 10.1371/journal.pgen.1006276
  • Peer Reviewed / Open Access
• [Journal Article] Complementary role of CNNM2 in sperm motility and Ca(2+) influx during capacitation. (2016)
  • Author(s): Yamazaki D, Funato Y, Miyata H, Ikawa M, Miki H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 474 Issue: 3 Pages: 441-446
  • DOI: 10.1016/j.bbrc.2016.05.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Mg2+ transporter CNNM4 regulates sperm Ca2+ homeostasis and it is essential for reproduction (2016)
  • Author(s): Daisuke Yamazaki, Haruhiko Miyata, Yosuke Funato, Yoshitaka Fujihara, Masahito Ikawa, Hiroaki Miki
  • Journal Title: Journal of Cell Science Volume: 未定 Issue: 9 Pages: 1940-1949
  • DOI: 10.1242/jcs.182220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Basolateral sorting of the Mg2+ transporter CNNM4 requires interaction with AP-1A and AP-1B. (2014)
  • Author(s): Hirata Y, Funato Y, Miki H.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 455 Issue: 3-4 Pages: 184-189
  • DOI: 10.1016/j.bbrc.2014.10.138
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Membrane Protein CNNM4-Dependent Mg2+ Efflux Suppresses Tumor Progression (2014)
  • Author(s): Yosuke Funato, Daisuke Yamazaki, Shin Mizukami, Lisa Du, Kazuya Kikuchi, Hiroaki Miki
  • Journal Title: J. Clin. Invest. Volume: 124 Issue: 12 Pages: 5398-5410
  • DOI: 10.1172/jci76614
  • Peer Reviewed
• [Journal Article] Reconstruction of insulin signal flow from phosphoproteome and metabolome data (2014)
  • Author(s): Yugi, K., Kubota, H., Toyoshima, Y., Noguchi, R., Kawata, K., Komori, Y., Uda, S., Kunida, K., Tomizawa, Y., Funato, Y., Miki, H., Matsumoto, M., Nakayama, K.I., Kashikura, K., Endo, K., Ikeda, K., Soga, T., Kuroda, S.
  • Journal Title: Cell Rep. Volume: 8 Issue: 4 Pages: 1171-1183
  • DOI: 10.1016/j.celrep.2014.07.021
  • NAID: 120005537752
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mg2+-dependent interactions of ATP with the cystathionine-β-synthase (CBS) domains of a magnesium transporter. (2014)
  • Author(s): Hirata Y, Funato Y, Takano Y, Miki H.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 21 Pages: 14731-14739
  • DOI: 10.1074/jbc.m114.551176
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] CNNM magnesium transporters in health and disease (2017)
  • Author(s): Funato, Y., Yamazaki, D., and Miki, H.
  • Organizer: IUPS 38th world congress
  • Int'l Joint Research / Invited
• [Presentation] PRLは細胞競合の悪用により上皮細胞の浸潤を促す (2016)
  • Author(s): 船戸 洋佑、山崎 大輔、三木 裕明
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] PRLによる細胞内Mg2+量の調節とその破綻によるがん悪性化 (2016)
  • Author(s): 船戸 洋佑、山崎 大輔、三木 裕明
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-09-27
  • Invited
• [Presentation] CNNM4によるMg2+排出は細胞のエネルギー状態を制御することでがん悪性化を防ぐ (2015)
  • Author(s): 船戸洋佑、山崎大輔、三木裕明
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Mg2+-efflux by MagEx and its suppression of tumor progression (2014)
  • Author(s): Funato, Y., Yamazaki, D. and Miki, H.
  • Organizer: 第11回プロテインホスファターゼ国際カンファレンス
  • Place of Presentation: 東北大学医学系研究科 東北大学艮陵会館
  • Year and Date: 2014-11-13
  • Invited