Elucidation of the mechanism of intracellular phosphatidylinositol trafficking by the Phs1 family

2010 Fiscal Year Final Research Report

• Project/Area Number: 20687008
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Hokkaido University
• Principal Investigator: KIHARA Akio Hokkaido University, 大学院・薬学研究院, 教授 (50333620)
• Co-Investigator(Renkei-kenkyūsha): SASSA Takayuki 北海道大学, 大学院・薬学研究院, 講師 (20342793) ; OBARA Keisuke 北海道大学, 大学院・薬学研究院, 助教 (30419858)
• Project Period (FY): 2008 – 2010
• Keywords: 脂質 / 代謝 / 細胞内輸送 / 脂肪酸 / 極長鎖脂肪酸 / スフィンゴ脂質 / 遺伝子 / タンパク質

Research Abstract

Phs1 is a 3-hydroxyacyl-CoA dehydratase involved in the elongation of very long-chain fatty acids (VLCFAs). We demonstrated here that Phs1 regulates sphingolipid synthesis and phosphatidylinositol transport through interacting with proteins involved in lipid metabolism and vesicular transport. We also succeeded in identifying mammalian homologs of Phs1, HACD1-4. By revealing substrate specificities of enzymes catalyzing the rate-limiting step of the VLCFA elongation, we have elucidated the entire VLCFA pathways in mammals. Moreover, we obtained some knowledge about relationship between VLCFA elongation and certain disorders.

Research Products

• [Journal Article] ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis. (2010)
  • Author(s): Ohno, Y., Suto, S., Yamanaka, M., Mizutani, Y., Mitsutake, S., Igarashi, Y., Sassa, T., Kihara, A.
  • Journal Title: Proc.Natl.Acad.Sci.USA 107 Pages: 18439-18444
  • Peer Reviewed
• [Journal Article] Hetero-oligomeric interactions of an ELOVL4 mutant protein : implications in the molecular mechanism of Stargardt-3 macular dystrophy. (2010)
  • Author(s): Okuda, A., Naganuma, T., Ohno, Y., Abe, K., Yamagata, M., Igarashi, Y., Kihara, A.
  • Journal Title: Mol.Vis. 16 Pages: 2438-2445
  • Peer Reviewed
• [Journal Article] Characterization of HACD1 K64Q mutant found in arrhythmogenic right ventricular dysplasia patients. (2010)
  • Author(s): Konishi, H., Okuda, A., Ohno, Y., Kihara, A.
  • Journal Title: J.Biochem. 148 Pages: 617-622
  • Peer Reviewed
• [Journal Article] 脂肪酸の多彩な代謝,生理機能と関連疾患 (2010)
  • Author(s): 木原章雄
  • Journal Title: 生化学 82 Pages: 591-605
• [Journal Article] Ceramide biosynthesis in keratinocyte and its role in skin function. (2009)
  • Author(s): Mizutani, Y., Mitsutake, S., Tsuji, K., Kihara, A., Igarashi, Y.
  • Journal Title: Biochimie 91 Pages: 784-790
  • Peer Reviewed
• [Journal Article] Membrane topology and essential amino acid residues of Phs1, a 3-hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid elongation. (2008)
  • Author(s): Kihara, A., Sakuraba, H., Ikeda, M., Denpoh, A., Igarashi, Y.
  • Journal Title: J.Biol.Chem. 283 Pages: 11199-11209
  • Peer Reviewed
• [Journal Article] Characterization of four mammalian 3-hydroxyacyl-CoA dehydratases involved in very long-chain fatty acid synthesis. (2008)
  • Author(s): Ikeda, M., Kanao, Y., Yamanaka, M., Sakuraba, H., Mizutani, Y., Igarashi, Y., Kihara, A.
  • Journal Title: FEBS Lett. 582 Pages: 2435-2440
  • Peer Reviewed
• [Journal Article] 2-Hydroxy-ceramide synthesis by ceramide synthase family : enzymatic basis for the preference of FA chain length. (2008)
  • Author(s): Mizutani, Y., Kihara, A., Chiba, H., Tojo, H., Igarashi, Y.
  • Journal Title: J.Lipid Res. 49 Pages: 2356-2364
  • Peer Reviewed
• [Presentation] C24アシルCoAの産生とC24セラミド合成による制御機構 (2010)
  • Author(s): 木原章雄
  • Organizer: 第3回セラミド研究会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-12
• [Presentation] Specificity of elongation of saturated, very long-chain fatty acids provides a link to C24 sphingolipid synthesis. (2010)
  • Author(s): Kihara, A.
  • Organizer: The 27th Naito Conference on Membrane Dynamics and Lipid Biology [I]
  • Place of Presentation: Sapporo
  • Year and Date: 2010-06-30
• [Presentation] Synthesis of very long-chain fatty acid and its relationship to sphingolipid metabolism. (2009)
  • Author(s): Kihara, A., Igarashi, Y.
  • Organizer: 50th International Conference on the Bioscience of Lipids
  • Place of Presentation: Regensburg, Germany
  • Year and Date: 2009-09-04
• [Remarks] ホームページ等
  • URL: http://www.pharm.hokudai.ac.jp/seika/index.html