The organelle quality control in the fatty acid beta-oxidation disorder

• Project/Area Number: 26860830
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Fujita Health University
• Principal Investigator: MORIYAMA Yohsuke 藤田保健衛生大学, 医学部, 助教 (00452532)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 脂肪酸代謝異常症 / ミトコンドリア / ミトコンドリアDNA / ペルオキシソーム / 連続スライスSEM / クリステ

Outline of Final Research Achievements

This study aimed to show how fatty acid β-oxidation disorder (FAOD) induce the mitochondrial damage, and tend to contribute the development of drags or treatment for FAOD. Our previous data showed that the mitochondrial respiratory chain disorder causes rapid and transient reduction of mitochondrial DNA amount. However, the fibroblasts of FAOD patients did not showed distinguished reduction of mitochondrial DNA, even in the glucose depleted condition. Then we tried to observe the ultrafine three-dimensional structure of the peroxisome and mitochondria in the rat organ and human culture cell using serial slice SEM. They are key organelles for fatty acid oxidation. We observed the three-dimensional morphology, distribution and the mode of fission of the peroxisome, and the structure of mitochondrial inner membrane.

Research Products

• [Journal Article] A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain deficiency. (2016)
  • Author(s): Kohda M, Mizuno Y, Hirata T, Yatsuka Y, Yamashita, Okuda A, Borna NN, Banshoya K, Ohnuma K, Suzuki T, Nagao A, Maehata H, Matsuda F, Higasa K, Nagasaki M, Yasuda J, Yamamoto M, Fushimi T, Shimura M, Kaiho-Ichimoto K, Harashima H, Yamazaki T, Mori M, Murayama K, Ohtake A, Okazaki Y.
  • Journal Title: PLoS Genetics: Volume: 12(1) Issue: 1 Pages: e1005679-e1005679
  • DOI: 10.1371/journal.pgen.1005679
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Diagnosis and molecular basis of mitochondrial respiratory chain disorders: Exome sequencing for disease gene identification (2014)
  • Author(s): Ohtake A, Murayama K, Mori M, Harashima H, Yamazaki T, Tamaru S, Yamashita Y, Kishita Y, Nakachi Y, Kohda M, Tokuzawa Y, Mizuno Y, Moriyama Y, Kato H, Okazaki Y.
  • Journal Title: Biochim Biophys Acta. Volume: 1840 Issue: 4 Pages: 1355-1359
  • DOI: 10.1016/j.bbagen.2014.01.025
  • Peer Reviewed
• [Journal Article] New genetic MT-ND6 and NDUFA1mutations in Mitochondrial Respiratory Chain Disorders. (2014)
  • Author(s): Uehara N, Mori M, Tokuzawa Y, Mizuno Y, Tamaru S, Kohda M, Moriyama Y, Nakachi Y, Matoba N, Yamazaki T, Harashima H, Murayama K, Hattori K, Hayashi J, Yamagata T, Fujita Y, Ito M, Tanaka M, Nibu K, Ohtake A, Okazaki Y.
  • Journal Title: Annals of Clinical and Translational Neurology Volume: 1 Issue: 5 Pages: 361-369
  • DOI: 10.1002/acn3.59
  • Peer Reviewed / Open Access
• [Journal Article] The first case in Asia of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (HSD10 disease) with atypical presentation. (2014)
  • Author(s): Fukao T, Akiba K, Goto M, Kuwayama N, Morita M, Hori T, Aoyama Y, Venkatesan R, Wierenga R, Moriyama Y, Hashimoto T, Usuda N, Murayama K, Ohtake A, Hasegawa Y, ShigematsuY, Hasegawa Y.
  • Journal Title: J Hum Genet Volume: 59 Issue: 11 Pages: 609-614
  • DOI: 10.1038/jhg.2014.79
  • NAID: 40020269650
  • Peer Reviewed
• [Presentation] 連続スライスSEMと組織化学的手法を用いた三次元超微構造観察技術によるペルオキシソーム分裂・増殖の解析 (2015)
  • Author(s): 森山陽介、深澤元晶、新美元、臼田信光
  • Organizer: 第31回医学生物学顕微鏡技術学会
  • Place of Presentation: 名古屋市立大学
  • Year and Date: 2015-06-20
• [Presentation] 超高圧電子顕微鏡と連続スライスSEMによる細胞小器官の三次元超微構造解析の試み (2015)
  • Author(s): 森山陽介、厚沢季美江、榎本早希子、荒井重勇、臼田信光
  • Organizer: 第71回顕微鏡学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2015-05-13
• [Presentation] 連続ブロック表面走査型電子顕微鏡(SBF-SEM)を用いた三次元超微構造観察によるペルオキシソーム分裂・増殖の解析 (2015)
  • Author(s): 森山陽介、臼田信光、深澤元晶、宮崎直幸、村田和義
  • Organizer: 第130回日本解剖学会全国学術集会
  • Place of Presentation: 兵庫、神戸、神戸国際会議場
  • Year and Date: 2015-03-21
• [Presentation] SBF-SEM Observation on Histochemically Stained Specimens­Three Dimensional Analyses of Peroxisomal Proliferations­ (2015)
  • Author(s): 森山陽介、宮崎直幸、村田和義、深澤元晶、臼田信光
  • Organizer: IGER International Symposium on Frontiers in Biological Research with
  • Place of Presentation: 愛知、名古屋、名古屋大学ES総合館
  • Year and Date: 2015-01-15
• [Presentation] 組織化学的手法を応用したSBF-SEMによるペルオキシゾーム分裂の三次元超微構造観察 (2014)
  • Author(s): 森山陽介、臼田信光、宮崎直幸、村田和義、深澤元晶
  • Organizer: 生理研研究会「電子顕微鏡機能イメージングの医学・生物学への応用」
  • Place of Presentation: 愛知、岡崎、岡崎コンファレンスセンター
  • Year and Date: 2014-11-13
• [Presentation] SBF-SEMによるペルオキシゾーム増殖の電顕組織化学的観察 (2014)
  • Author(s): 森山陽介、臼田信光、深澤元晶、宮崎直幸、村田和義
  • Organizer: 第46回日本臨床分子形態学会総会・学術集会
  • Place of Presentation: 東京、新宿、TKP市ヶ谷カンファレンスセンター
  • Year and Date: 2014-10-18