Analysis of molecular mechanisms underlying the diversity of very long-chain fatty acid synthesis and the muscle development.

• Project/Area Number: 25870001
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; Cell biology
• Research Institution: Hokkaido University
• Principal Investigator: OHNO Yusuke 北海道大学, 薬学研究科(研究院), 助教 (50611498)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 極長鎖脂肪酸 / 筋分化 / ミオパチー / 3-ヒドロキシアシルCoA脱水酵素 / HACD / 3-ヒドロキシルアシルCoA脱水酵素 / 多価不飽和脂肪酸

Outline of Final Research Achievements

Fatty acids with a carbon (C) chain-length longer than 20 are called very long-chain fatty acids (VLCFAs). Although amounts of VLCFAs are quite smaller than that of long chain fatty acids (LCFAs) in organisms, VLCFAs exert a variety of biological functions that are not complemented by LCFAs. HACD family proteins (HACD1-4) catalyze a dehydration reaction in the VLCFAs elongation cycle, yet the biological functions of HACD family proteins have remained elusive. In this project, we investigated the roles of VLCFAs and HACD1 in the muscle development by using yeasts, mammalian cells, HACD1 knockout mice, and human biopsies as experimental materials, and we discovered that human HACD1 gene mutation causes myopathy. Furthermore, we demonstrated that HACD1 is involved in the synthesis of C24:1 fatty acid, regulation of membrane fluidity, and cell fusion during myogenesis.

Research Products

• [Journal Article] Congenital myopathy is caused by mutation of HACD1 (2013)
  • Author(s): Muhammad E, Reish O, Ohno Y, Scheetz T, Deluca A, Searby C, Regev M, Benyamini L, Fellig Y, Kihara A, Sheffield VC, Parvari R
  • Journal Title: Hum. Mol. Genet. Volume: 22 Issue: 25 Pages: 5229-5236
  • DOI: 10.1093/hmg/ddt380
  • Peer Reviewed
• [Journal Article] Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile (2013)
  • Author(s): Abe K, Ohno Y, Sassa T, Taguchi R, Çali şkan, M, Ober C, Kihara A
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 51 Pages: 36741-36749
  • DOI: 10.1074/jbc.m113.493221
  • NAID: 120005385316
  • Peer Reviewed
• [Remarks] 北海道大学 薬学研究院 生化学研究室 研究概要
  • URL: http://www.pharm.hokudai.ac.jp/seika/researches/3.html
• [Remarks] 北海道大学 薬学研究院 生化学研究室 研究成果（大野祐介）
  • URL: http://www.pharm.hokudai.ac.jp/seika/publications/Ohno.html
• [Remarks] 北海道大学 大学院薬学研究院 生化学研究室
  • URL: http://www.pharm.hokudai.ac.jp/seika/index.html