Elucidation of a novel pool mechanism of B vitamins through lysosome accumulation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18KK0453
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Nagoya City University
• Principal Investigator: Yasujima Tomoya 名古屋市立大学, 医薬学総合研究院(薬学), 講師 (50753555)
• Project Period (FY): 2018 – 2020
• Keywords: トランスポーター / リソソーム / ピリドキシン / ビタミンプール

Outline of Final Research Achievements

As a result of detailed functional analysis of the novel transporter lysosomal multivitamin transporter 1 (LMVT1), the pyridoxine transport mediated by LMVT1 was driven by cotransport with protons. It was suggested to play a role in supplying pyridoxine from lysosomes into the cytoplasm, suggesting that it may be involved in the excretion and transport of various vitamins including pyridoxine from lysosome in an acidic environment to cytoplasm in a neutral pH environment. In addition, when the substrate recognition of LMVT1 was investigated, it was found that LMVT1 also transports compounds other than vitamins (drugs and bioactive substances). Taken these finding, LMVT1 may be involved in the regulation of pharmacokinetics and various physiological functions.

Free Research Field

薬物動態制御学

Academic Significance and Societal Importance of the Research Achievements

生体において、葉酸（ビタミンB9）の細胞内プール機構の存在は知られていたが、本研究成果は、葉酸以外の水溶性ビタミンにおいても、細胞内にプールされる機構が備わっていることを強く示唆するものである。この知見は、世界で初めて見出されたものであり、学術的意義は非常に高いと考えられる。また、本知見を応用することにより、効果的なビタミン摂取法の提案が可能になると期待され、社会的意義も大きいと考えられる。