Transport mechanism of very long chain fatty acyl-CoA into peroxisomes mediated by peroxisomal ABC protein ABCD1

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14900
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: University of Toyama
• Principal Investigator: Kawaguchi Kosuke 富山大学, 学術研究部薬学・和漢系, 助教 (80624866)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: ABCタンパク質 / ペルオキシソーム / 極長鎖脂肪酸CoA / プロテオリポソーム / メタノール資化性酵母

Outline of Final Research Achievements

Dysfunction of peroxisomal ATP-binding cassette (ABC) protein, ABCD1, causes a severe neurodegenerative disease, X-linked adrenoleukodystophy. ABCD1 is suggested to be involved in the transport of very long chain fatty acyl-CoA, but the precise mechanism of the transport has yet to be elucidated.
It is demonstrated that ABCD1 transports very long chain fatty acyl-CoA as free very long chain fatty acid into peroxisomes through the hydrolysis of very long chain fatty acyl-CoA mediated by the acyl-CoA thioesterase activity of ABCD1 itself and that acyl-CoA thioesterase activity of ABCD1 is indispensable for this transport system.

Free Research Field

生化学・分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

ヒトABCD1のもつATPase活性とアシルCoAチオエステラーゼ活性が協調して極長鎖脂肪酸CoAをペルオキシソーム内へと輸送する分子機構について初めて明らかとした。また、蛍光基NBDで標識したNBD-パルミトイルCoAを基質として用いることで、ABCD1が加水分解された遊離脂肪酸を輸送基質とすることを直接検出することに初めて成功した。