OOSAKI Yuuki

写真a

Affiliation

School of Medicine, Department of Anatomy (1)

Job title

Professor
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Degree 【 display / non-display 】

  • Tottori University   Ph.D. (Life Science)

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Research Experience 【 display / non-display 】

  • 2021.09
    -
    Now

    Sapporo Medical University   School of Medicine, Department of Anatomy I   Professor

  • 2017.06
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    2021.08

    Nagoya University Graduate School of Medicine   Department of Anatomy and Molecular Cell Biology   Associate Proferssor

  • 2014.07
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    2017.05

    Nagoya University Graduate School of Medicine   Department of Anatomy and Molecular Cell Biology   Lecturer

  • 2012.04
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    2014.06

    Nagoya University Graduate School of Medicine   Department of Anatomy and Molecular Cell Biology   Assistant Professor

  • 2010.04
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    2012.03

    University of Helsinki   Department of Anatomy, Faculty of Medicine   postdoctoral researcher

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Professional Memberships 【 display / non-display 】

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    日本細胞生物学会

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    日本解剖学会

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    日本組織細胞化学会

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    日本生化学会

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Research Areas 【 display / non-display 】

  • Life sciences   Anatomy  

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Research Interests 【 display / non-display 】

  • Lipid metabolism

  • Hepatocytes

  • Vesicle transport

  • Lipid droplets

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Papers 【 display / non-display 】

  • Distinct features of two lipid droplets types in cell nuclei from patients with liver diseases

    Norihiro Imai, Yuki Ohsaki, Jinglei Cheng, Jingjing Zhang, Fumitaka Mizuno, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Masatoshi Ishigami, Hiroaki Wake, Hiroki Kawashima

    Scientific Reports ( Springer Science and Business Media LLC )  13 ( 1 )  2023.04

    Authorship：   Lead author  , Corresponding author

    　View Summary

    Abstract Lipid droplets (LDs) have been observed in the nuclei of hepatocytes; however, their significance in liver disease remains unresolved. Our purpose was to explore the pathophysiological features of intranuclear LDs in liver diseases. We included 80 patients who underwent liver biopsies; the specimens were dissected and fixed for electron microscopy analysis. Depending on the presence of adjacent cytoplasmic invagination of the nuclear membrane, LDs in the nuclei were classified into two types: nucleoplasmic LDs (nLDs) and cytoplasmic LD invagination with nucleoplasmic reticulum (cLDs in NR). nLDs were found in 69% liver samples and cLDs in NR were found in 32%; no correlation was observed between the frequencies of the two LD types. nLDs were frequently found in hepatocytes of patients with nonalcoholic steatohepatitis, whereas cLDs in NR were absent from the livers of such patients. Further, cLDs in NR were often found in hepatocytes of patients with lower plasma cholesterol level. This indicates that nLDs do not directly reflect cytoplasmic lipid accumulation and that formation of cLDs in NR is inversely correlated to the secretion of very low-density lipoproteins. Positive correlations were found between the frequencies of nLDs and endoplasmic reticulum (ER) luminal expansion, suggesting that nLDs are formed in the nucleus upon ER stress. This study unveiled the presence of two distinct nuclear LDs in various liver diseases.

    DOI

  • Oleic acid‐bound <scp>FABP7</scp> drives glioma cell proliferation through regulation of nuclear lipid droplet formation

    Banlanjo Abdulaziz Umaru, Yoshiteru Kagawa, Yuki Ohsaki, Yijun Pan, Chuck T. Chen, Daniel K. Chen, Toshiaki Abe, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Motoko Maekawa, Yui Yamamoto, Tunyanat Wannakul, Shuhan Yang, Richard P. Bazinet, Yuji Owada

    The FEBS Journal ( Wiley )  290 ( 7 ) 1798 - 1821  2022.11

    DOI

  • Oxygen-Glucose Deprivation Decreases the Motility and Length of Axonal Mitochondria in Cultured Dorsal Root Ganglion Cells of Rats.

    Shin Kikuchi, Takayuki Kohno, Takashi Kojima, Haruyuki Tatsumi, Yuki Ohsaki, Takafumi Ninomiya

    Cellular and molecular neurobiology    2022.06  [International journal]

    　View Summary

    Controlling axonal mitochondria is important for maintaining normal function of the neural network. Oxygen-glucose deprivation (OGD), a model used for mimicking ischemia, eventually induces neuronal cell death similar to axonal degeneration. Axonal mitochondria are disrupted during OGD-induced neural degeneration; however, the mechanism underlying mitochondrial dysfunction has not been completely understood. We focused on the dynamics of mitochondria in axons exposed to OGD; we observed that the number of motile mitochondria significantly reduced in 1 h following OGD exposure. In our observation, the decreased length of stationary mitochondria was affected by the following factors: first, the halt of motile mitochondria; second, the fission of longer stationary mitochondria; and third, a transformation from tubular to spherical shape in OGD-exposed axons. Motile mitochondria reduction preceded stationary mitochondria fragmentation in OGD exposure; these conditions induced the decrease of stationary mitochondria in three different ways. Our results suggest that mitochondrial morphological changes precede the axonal degeneration while ischemia-induced neurodegeneration.

    DOI PubMed

  • Nuclear lipid droplets form in the inner nuclear membrane in a seipin-independent manner.

    Kamil Sołtysik, Yuki Ohsaki, Tsuyako Tatematsu, Jinglei Cheng, Asami Maeda, Shin-Ya Morita, Toyoshi Fujimoto

    The Journal of cell biology   220 ( 1 )  2021.01  [Refereed]  [International journal]

    　View Summary

    Nuclear lipid droplets (LDs) in hepatocytes are derived from precursors of very-low-density lipoprotein in the ER lumen, but it is not known how cells lacking the lipoprotein secretory function form nuclear LDs. Here, we show that the inner nuclear membrane (INM) of U2OS cells harbors triglyceride synthesis enzymes, including ACSL3, AGPAT2, GPAT3/GPAT4, and DGAT1/DGAT2, and generates nuclear LDs in situ. mTOR inhibition increases nuclear LDs by inducing the nuclear translocation of lipin-1 phosphatidic acid (PA) phosphatase. Seipin, a protein essential for normal cytoplasmic LD formation in the ER, is absent in the INM. Knockdown of seipin increases nuclear LDs and PA in the nucleus, whereas seipin overexpression decreases these. Seipin knockdown also up-regulates lipin-1β expression, and lipin-1 knockdown decreases the effect of seipin knockdown on nuclear LDs without affecting PA redistribution. These results indicate that seipin is not directly involved in nuclear LD formation but instead restrains it by affecting lipin-1 expression and intracellular PA distribution.

    DOI PubMed

  • Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets.

    Yuta Ogasawara, Jinglei Cheng, Tsuyako Tatematsu, Misaki Uchida, Omi Murase, Shogo Yoshikawa, Yuki Ohsaki, Toyoshi Fujimoto

    Nature communications   11 ( 1 ) 4480 - 4480  2020.09  [Refereed]  [International journal]

    　View Summary

    Macroautophagy initiates by formation of isolation membranes, but the source of phospholipids for the membrane biogenesis remains elusive. Here, we show that autophagic membranes incorporate newly synthesized phosphatidylcholine, and that CTP:phosphocholine cytidylyltransferase β3 (CCTβ3), an isoform of the rate-limiting enzyme in the Kennedy pathway, plays an essential role. In starved mouse embryo fibroblasts, CCTβ3 is initially recruited to autophagic membranes, but upon prolonged starvation, it concentrates on lipid droplets that are generated from autophagic degradation products. Omegasomes and isolation membranes emanate from around those lipid droplets. Autophagy in prolonged starvation is suppressed by knockdown of CCTβ3 and is enhanced by its overexpression. This CCTβ3-dependent mechanism is also present in U2OS, an osteosarcoma cell line, and autophagy and cell survival in starvation are decreased by CCTβ3 depletion. The results demonstrate that phosphatidylcholine synthesis through CCTβ3 activation on lipid droplets is crucial for sustaining autophagy and long-term cell survival.

    DOI PubMed

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Misc 【 display / non-display 】

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Research Projects 【 display / non-display 】

  • 脂肪滴の核内での形成機構と生理機能の形態学的解析

    Project Year :

    2023.04
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    2025.03
     

    大﨑雄樹

    Authorship： Principal investigator

  • 核内脂肪滴の肝疾患における意義

    Project Year :

    2023.04
    -
    2025.03
     

    大﨑雄樹

    Authorship： Principal investigator

  • 核膜変形機構と核内脂質代謝の細胞老化への影響の解明

    Project Year :

    2023.04
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    2024.03
     

    大﨑雄樹

    Authorship： Principal investigator

  • 脂肪滴による核内蛋白質機能制御機構の解明

    Project Year :

    2022.08
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    2027.05
     

    大﨑雄樹

    Authorship： Principal investigator

  • Elucidation of nuclear lipid droplet functions

    Grant-in-Aid for Scientific Research (A)

    Project Year :

    2022.04
    -
    2025.03
     

    藤本豊士, 大﨑雄樹, 辻琢磨

    Authorship： Coinvestigator(s)

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Presentations 【 display / non-display 】

  • 脂肪滴の新たな核内生理機能プラットフォームとしての 可能性

    大﨑 雄樹, 和田 亘弘, 程 晶磊, 今井 則博  [Invited]

    第128回日本解剖学会総会・全国学術集会 

    Presentation date： 2023.03

    Event date：
    2023.03
    　
    　

  • 肝疾患における脂肪滴の異所性形成

    大﨑 雄樹, 今井 則博, 程 晶磊, 立松 寛人, 菊地 鴻太

    第54回日本臨床分子形態学会 

    Presentation date： 2022.11

    Event date：
    2022.11
    　
    　

  • 核内脂肪滴形成を制御する新たな分子機序

    大﨑 雄樹

    日本解剖学会第68回東北北海道支部学術集会 

    Presentation date： 2022.09

    Event date：
    2022.09
    　
    　

  • 脂肪滴の核内での生理的意義

    大﨑 雄樹  [Invited]

    第64回日本脂質生化学会 

    Presentation date： 2022.06

    Event date：
    2022.06
    　
    　

  • 脂肪滴の核内形成機序に影響する核膜形態制御分子の検索

    大崎 雄樹, 立松 寛人, 程 晶磊

    第127回日本解剖学会総会・全国学術集会 

    Presentation date： 2022.03

    Event date：
    2022.03
    　
    　

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