Pathogenic mechanism of peroxisome biogenesis disorder

2016 Fiscal Year Final Research Report

• Project/Area Number: 24247038
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: Fujiki Yukio 九州大学, 生体防御医学研究所, 特任教授 (70261237)
• Co-Investigator(Kenkyū-buntansha): 田村 茂彦 九州大学, 基幹教育院, 教授 (90236753)
• Co-Investigator(Renkei-kenkyūsha): HONSHO MASANORI 九州大学, 生体防御医学研究所, 特任准教授 (90372747) ; OKUMOTO KANJI 九州大学, 大学院理学研究院, 助教 (20363319) ; YAMAMOTO NOBUHIKO 大阪大学, 大学院生命機能研究科, 教授 (00191429)
• Research Collaborator: YAMASHITA TOSHIHIDE 大阪大学, 医学系研究科, 教授 (10301269)
• Project Period (FY): 2012-05-31 – 2017-03-31
• Keywords: ペルオキシソーム / ペルオキシソーム欠損症 / Zellweger症候群 / 中枢神経系障害 / 代謝調節 / プラスマローゲン / コレステロール / リピドーム解析

Outline of Final Research Achievements

Peroxisomal disorders caused by defects in peroxisome biogenesis, peroxisomal β-oxidation, or biosynthesis of plasmalogens manifest severe neural disorders of the central nervous system (CNS). Their molecular pathogenesis remains to be elucidated. In this research, we showed that peroxisomal metabolism was essential for not only the morphogenesis but also the integrity of CNS. The impairment of a secretory factor essential for the morphogenesis of CNS was found in the mouse defective in peroxisome biogenesis. We also proposed the relationship between pathological phenotype and defect of peroxisomal metabolisms using fibroblasts from the patients with peroxisomal biogenesis disorders and peroxisomal single enzyme deficiency diseases. Furthermore, we also reported that the plasmalogen-dependent regulation of cholesterol biosynthesis and release of catalase, a peroxisomal matrix enzyme, from peroxisomes to the cytosol upon the oxidative stress.

Free Research Field

分子細胞生物学, 生化学