OHBA Yohsuke

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 代謝生理化学講座 ( Shiba-Kyoritsu )

Position

Assistant Professor/Senior Assistant Professor

Contact Address

東京都港区芝公園1-5-30

Career 【 Display / hide 】

  • 2015.04
    -
    2016.01

    東京大学, 薬学系研究科, 助教

  • 2016.02
    -
    2020.09

    Max Planck Institute for Biology of Ageing, ポストドクトラルフェロー

  • 2020.10
    -
    2022.04

    武田薬品工業, 研究員

  • 2022.05
    -
    Present

    慶應義塾大学, 薬学部, 専任講師

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Academic Background 【 Display / hide 】

  • 2006.04
    -
    2010.03

    The University of Tokyo, Pharmaceutical Sciences, 薬学科

    University, Graduated

  • 2010.04
    -
    2012.03

    The University of Tokyo, 薬学系研究科

    Graduate School, Completed, Master's course

  • 2012.04
    -
    2015.03

    The University of Tokyo, 薬学系研究科

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士(薬科学), The University of Tokyo, Coursework, 2015.03

    小胞体ストレス応答分子IRE1を介した膜脂肪酸ストレス応答機構の解明

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Research Areas 【 Display / hide 】

  • Life Science / Cell biology

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Research Keywords 【 Display / hide 】

  • ミトコンドリア

  • リン脂質

  • 脂質輸送タンパク質

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Papers 【 Display / hide 】

  • Mitochondrial cardiolipin remodeling facilitates efficient myoblast differentiation

    Ohba Y., Fujiwara C.A., Arita M.

    Journal of Lipid Research 66 ( 11 )  2025.11

    ISSN  00222275

    　View Summary

    During myoblast differentiation, mitochondria undergo dynamic changes in their morphology and function. Although the mitochondrial membrane lipid environment is closely related to mitochondrial integrity, how mitochondrial lipid composition changes during myoblast differentiation and whether it is involved in efficient differentiation remains unclear. In this study, we applied LC-MS/MS-based untargeted lipidomics to the mitochondria isolated from C2C12 murine myoblasts and found that the proportion of linoleic acid (C18:2)containing cardiolipin (CL) increased during the early stages of differentiation. In parallel, the expression of tafazzin, a mitochondrial CL remodeling enzyme, increased in line with myoblast differentiation. Notably, the increase in C18:2-containing CL was not suppressed by the knockdown of MyoD (myoblast determination protein 1), a master transcription factor for myoblast differentiation. In contrast, the inhibition of CL biosynthesis and remodeling significantly suppressed differentiation progression, which was partially rescued by exogenous supplementation with C18:2. Similar trends in CL remodeling were observed when primary stem cells isolated from mouse skeletal muscle differentiated into myotubes. These results demonstrate that mitochondrial CL remodeling at an early stage is required to promote efficient myoblast differentiation.

  • Characterization of UGT8 as a monogalactosyl diacylglycerol synthase in mammals

    Ohba Y., Motohashi M., and Arita M.

    The journal of Biochemistry 177 ( 2 ) 141 - 152 2024.12

    Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  0021924X

    　View Summary

    Monogalactosyl diacylglycerol (MGDG) is a major membrane lipid component in plants and is crucial for proper thylakoid functioning. However, MGDG in mammals has not received much attention, partly because of its relative scarcity in mammalian tissues. In addition, the biosynthetic pathway of MGDG in mammals has not been thoroughly analysed, although some reports have suggested that UGT8, a ceramide galactosyltransferase, has the potential to catalyse MGDG biosynthesis. Here, we successfully captured the endogenous levels of MGDG in HeLa cells using liquid chromatography quadrupole time-of-flight mass spectrometry (LC–QTOF-MS)-based lipidomics. Cellular MGDG was completely depleted in CRISPR/Cas9-mediated UGT8 knockout (KO) HeLa cells. Transient overexpression of UGT8 enhanced MGDG production in HeLa cells, and the corresponding cell lysates displayed MGDG biosynthetic activity in vitro. Site-directed mutagenesis revealed that His358 within the UGT signature sequence was important for its activity. UGT8 was localized in the endoplasmic reticulum and activation of the unfolded protein response by membrane lipid saturation was impaired in UGT8 KO cells. These results demonstrate that UGT8 is an MGDG synthase in mammals and that UGT8 regulates membrane lipid saturation signals in cells.

  • Fluorescence Lifetime Imaging of Lipid Heterogeneity in the Inner Mitochondrial Membrane with a Super-photostable Environment-Sensitive Probe

    Wang J., Taki M., Ohba Y., Arita M., Yamaguchi S.

    Angewandte Chemie - International Edition 63 ( 28 )  2024.07

    Research paper (scientific journal), Accepted,  ISSN  14337851

    　View Summary

    The inner mitochondrial membrane (IMM) undergoes dynamic morphological changes, which are crucial for the maintenance of mitochondrial functions as well as cell survival. As the dynamics of the membrane are governed by its lipid components, a fluorescent probe that can sense spatiotemporal alterations in the lipid properties of the IMM over long periods of time is required to understand mitochondrial physiological functions in detail. Herein, we report a red-emissive IMM-labeling reagent with excellent photostability and sensitivity to its environment, which enables the visualization of the IMM ultrastructure using super-resolution microscopy as well as of the lipid heterogeneity based on the fluorescence lifetime at the single mitochondrion level. Combining the probe and fluorescence lifetime imaging microscopy (FLIM) showed that peroxidation of unsaturated lipids in the IMM by reactive oxygen species caused an increase in the membrane order, which took place prior to mitochondrial swelling.

  • Regulation of mitochondrial proteostasis by the proton gradient

    M Patron, D Tarasenko, H Nolte, L Kroczek, M Ghosh, Y Ohba, Y Lasarzewski, ZA Ahmadi, A Cabrera-Orefice, A Eyiama, T Kellermann, EI Rugarli, U Brandt, M Meinecke, T Langer

    The EMBO Journal 41 ( 16 ) e110476 2022.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  02614189

    　View Summary

    Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multiproteomic approach to demonstrate the regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+/H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.

  • Lipid signaling drives proteolytic rewiring of mitochondria by YME1L

    MacVicar, T.*, Ohba, Y.*, Nolte, H., Mayer, F.C., Tatsuta, T., Sprenger, HG., Lindner, B., Zhao, Y., Li, J., Bruns, C., Krüger, M., Habich, M., Riemer, J., Schwarzer, R., Pasparakis, M., Henschke, S., Brüning, J.C., Zamboni, N., and Langer, T.

    Nature  ( 575 ) 361 - 365 2019.11

    Research paper (scientific journal), Joint Work, Lead author, Accepted

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 酸素欠乏によるミトコンドリアタンパク質のリプログラミング

    大場陽介

    実験医学  ( 38 ) 995 - 998 2020

    Article, review, commentary, editorial, etc. (other), Single Work, Lead author

  • Regulation of mitochondrial plasticity by the i-AAA protease YME1L

    Ohba, Y., MacVicar, T. and and Langer, T.

    Biological Chemistry  ( 401 ) 877 - 890 2020

    Joint Work, Lead author

  • 脂質異常とオルガネラストレス

    大場陽介、河野望

    医学のあゆみ  ( 245 ) 382 - 388 2015

    Joint Work, Lead author

  • リン脂質脂肪酸鎖メタボロームと代謝疾患

    大場陽介、河野望、新井洋由

    内分泌・糖尿病・代謝内科  ( 41 ) 341 - 346 2015

    Joint Work

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 膜脂質環境によるミトコンドリアプロテアーゼ活性制御機構の解明

    2023.04
    -
    2026.03

    基盤研究(C), Principal investigator

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD: (PHYSIOLOGICAL CHEMISTRY AND METABOLISM)

    2025

  • SEMINAR: (PHYSIOLOGICAL CHEMISTRY AND METABOLISM)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2025

  • IMMUNOLOGY AND METABOLISM

    2025

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