Researcher Database

Yuta Ogasawara
Institute for Genetic Medicine Disease Control
Specially Appointed Assistant Professor

Researcher Profile and Settings


  • Institute for Genetic Medicine Disease Control

Job Title

  • Specially Appointed Assistant Professor

J-Global ID

Research Areas

  • Life sciences / Cell biology / Lipid metabolism
  • Life sciences / Cell biology / cell biology
  • Life sciences / Cell biology / Bioimaging
  • Life sciences / Cell biology / Autophagy

Academic & Professional Experience

  • 2022/04 - Today Hokkaido University
  • 2021/04 - 2022/03 公益財団法人微生物化学研究会 微生物化学研究所構造生物学研究部 博士研究員
  • 2020/10 - 2020/12 広島大学大学院 医系科学研究科ストレス分子動態学(住友電工 グループ社会貢献基金)寄附講座 寄附講座助教
  • 2019/06 - 2020/10 順天堂大学 老人性疾患病態・治療研究センター 博士研究員
  • 2015/05 - 2019/05 Nagoya University Graduate School of Medicine, Department of Anatomy and Molecular Cell Biology Specially Appointed Assistant Professor
  • 2015/04 - 2015/05 Nagahama Institute of Bio-Science and Technology. Graduate School of Biosciences Specially Appointed Research Assistant


  • 2010/04 - 2015/03  Nagahama Institute of Bio-Science and Technology  Graduate School of Biosciences
  • 2006/04 - 2010/03  Nagahama Institute of Bio-Science and Technology  faculty of Bio-Science  Department of Bio-Science

Association Memberships


Research Activities

Published Papers

  • Jin Cui, Yuta Ogasawara, Ikuko Kurata, Kazuaki Matoba, Yuko Fujioka, Nobuo N Noda, Masakatsu Shibasaki, Takumi Watanabe
    Journal of the American Chemical Society 2022/09/15 
    Selective modulation of autophagy is a promising therapeutic strategy, especially for cancer treatment. However, the lack of specific autophagy inhibitors limits this strategy. The formation of the ATG12-ATG5-ATG16L1 complex is essential for targeting the ATG12-ATG5 conjugate to proper membranes and to generate LC3-II for the progression of autophagy. Thus, targeting ATG5-ATG16L1 protein-protein interactions (PPIs) might inhibit early stage autophagy with high specificity. In this paper, we report that a stapled peptide derived from ATG16L1 exhibits potent binding affinity to ATG5, striking resistance to proteolysis, and significant autophagy inhibition activities in cells.
  • Minami Orii, Takuma Tsuji, Yuta Ogasawara, Toyoshi Fujimoto
    The Journal of cell biology 220 (3) 2021/03/01 
    The mechanism of isolation membrane formation in autophagy is receiving intensive study. We recently found that Atg9 translocates phospholipids across liposomal membranes and proposed that this functionality plays an essential role in the expansion of isolation membranes. The distribution of phosphatidylinositol 3-phosphate in both leaflets of yeast autophagosomal membranes supports this proposal, but if Atg9-mediated lipid transport is crucial, symmetrical distribution in autophagosomes should be found broadly for other phospholipids. To test this idea, we analyzed the distributions of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol 4-phosphate by freeze-fracture electron microscopy. We found that all these phospholipids are distributed with comparable densities in the two leaflets of autophagosomes and autophagic bodies. Moreover, de novo-synthesized phosphatidylcholine is incorporated into autophagosomes preferentially and shows symmetrical distribution in autophagosomes within 30 min after synthesis, whereas this symmetrical distribution is compromised in yeast expressing an Atg9 mutant. These results indicate that transbilayer phospholipid movement that is mediated by Atg9 is involved in the biogenesis of autophagosomes.
  • Yuta Ogasawara, Takuma Tsuji, Toyoshi Fujimoto
    Seminars in cell & developmental biology 108 47 - 54 2020/12 
    Lipid droplets (LDs) are not an inert storage of excessive lipids, but play various roles in cellular lipid metabolism. Autophagy involves several mechanisms for the degradation of cellular components, and is related to many aspects of lipid metabolism. LD and autophagic membranes often distribute in proximity, but their relationship is complex. LDs can be degraded by autophagy, but LDs are also generated as a result of autophagy or support the execution of autophagy. Moreover, several proteins crucial for autophagy were shown to affect different aspects of LD formation. This article aims to categorize this multifaceted and seemingly entangled LD-autophagy relationship and to discuss unresolved issues.
  • Yuta Ogasawara, Jinglei Cheng, Tsuyako Tatematsu, Misaki Uchida, Omi Murase, Shogo Yoshikawa, Yuki Ohsaki, Toyoshi Fujimoto
    Nature Communications 11 (1) 4480 - 4480 2020/12 [Refereed]
    Abstract 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.
  • Yuta Ogasawara, Shintaro Kira, Yukio Mukai, Takeshi Noda, Akitsugu Yamamoto
    BIOLOGY OPEN 6 (1) 35 - 40 2046-6390 2017/01 [Refereed][Not invited]
    Macroautophagy, a major degradation pathway of cytoplasmic components, is carried out through formation of a double-membrane structure, the autophagosome. Although the involvement of specific lipid species in the formation process remains largely obscure, we recently showed that mono-unsaturated fatty acids (MUFA) generated by stearoyl-CoA desaturase 1 (SCD1) are required for autophagosome formation in mammalian cells. To obtain further insight into the role of MUFA in autophagy, in this study we analyzed the autophagic phenotypes of the yeast mutant of OLE1, an orthologue of SCD1. Delta ole1 cells were defective in nitrogen starvation-induced autophagy, and the Cvt pathway, when oleic acid was not supplied. Defects in elongation of the isolation membrane led to a defect in autophagosome formation. In the absence of Ole1, the transmembrane protein Atg9 was not able to reach the pre-autophagosomal structure (PAS), the site of autophagosome formation. Thus, autophagosome formation requires Ole1 during the delivery of Atg9 to the PAS/autophagosome from its cellular reservoir.
  • Yuta Ogasawara, Eisuke Itakura, Nozomu Kono, Noboru Mizushima, Hiroyuki Arai, Atsuki Nara, Tamio Mizukami, Akitsugu Yamamoto
    JOURNAL OF BIOLOGICAL CHEMISTRY 289 (34) 23938 - 23950 0021-9258 2014/08 [Refereed][Not invited]
    Background: Autophagosome membranes are believed to have a high content of unsaturated fatty acids, but the roles of unsaturated fatty acids in autophagy are not clear. Results: Stearoyl-CoA desaturase 1 inhibitor 28c suppressed autophagy at the earliest stage of autophagosome formation. Conclusion: Unsaturated fatty acids are required for autophagosome formation. Significance: This study clarifies the importance of fatty acid desaturation in the autophagosome formation. Autophagy is one of the major degradation pathways for cytoplasmic components. The autophagic isolation membrane is a unique membrane whose content of unsaturated fatty acids is very high. However, the molecular mechanisms underlying formation of this membrane, including the roles of unsaturated fatty acids, remain to be elucidated. From a chemical library consisting of structurally diverse compounds, we screened for novel inhibitors of starvation-induced autophagy by measuring LC3 puncta formation in mouse embryonic fibroblasts stably expressing GFP-LC3. One of the inhibitors we identified, 2,5-pyridinedicarboxamide, N2,N5-bis[5-[(dimethylamino)carbonyl]-4-methyl-2-thiazolyl], has a molecular structure similar to that of a known stearoyl-CoA desaturase (SCD) 1 inhibitor. To determine whether SCD1 inhibition influences autophagy, we examined the effects of the SCD1 inhibitor 28c. This compound strongly inhibited starvation-induced autophagy, as determined by LC3 puncta formation, immunoblot analyses of LC3, electron microscopic observations, and p62/SQSTM1 accumulation. Overexpression of SCD1 or supplementation with oleic acid, which is a catalytic product of SCD1 abolished the inhibition of autophagy by 28c. Furthermore, 28c suppressed starvation-induced autophagy without affecting mammalian target of rapamycin activity, and also inhibited rapamycin-induced autophagy. In addition to inhibiting formation of LC3 puncta, 28c also inhibited formation of ULK1, WIPI1, Atg16L, and p62/SQSTM1 puncta. These results suggest that SCD1 activity is required for the earliest step of autophagosome formation.
  • K. Devereaux, C. Dall'Armi, Y. Ogasawara, X. Zhou, F. Wang, A. Yamamoto, G. Di Paolo
    MOLECULAR BIOLOGY OF THE CELL 23 (10) e76405  1059-1524 2012 [Refereed][Not invited]
  • Shusuke Yonekawa, Akiko Furuno, Takashi Baba, Yukio Fujiki, Yuta Ogasawara, Akitsugu Yamamoto, Mitsuo Tagaya, Katsuko Tani
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 108 (31) 12746 - 12751 0027-8424 2011/08 [Refereed][Not invited]
    Sec16 plays a key role in the formation of coat protein II vesicles, which mediate protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. Mammals have two Sec16 isoforms: Sec16A, which is a longer primary ortholog of yeast Sec16, and Sec16B, which is a shorter distant ortholog. Previous studies have shown that Sec16B, as well as Sec16A, defines ER exit sites, where coat protein II vesicles are formed in mammalian cells. Here, we reveal an unexpected role of Sec16B in the biogenesis of mammalian peroxisomes. When overexpressed, Sec16B was targeted to the entire ER, whereas Sec16A was mostly cytosolic. Concomitant with the overexpression of Sec16B, peroxisomal membrane biogenesis factors peroxin 3 (Pex3) and Pex16 were redistributed from peroxisomes to Sec16B-positive ER membranes. Knockdown of Sec16B but not Sec16A by RNAi affected the morphology of peroxisomes, inhibited the transport of Pex16 from the ER to peroxisomes, and suppressed expression of Pex3. These phenotypes were significantly reversed by the expression of RNAi-resistant Sec16B. Together, our results support the view that peroxisomes are formed, at least partly, from the ER and identify a factor responsible for this process.

Books etc

  • 『オートファジー』
    山本章嗣, 西野-林美都子, 小笠原裕太 (Contributor第14章 電子顕微鏡を用いたオートファジー解析)
    化学同人 2012/12

Conference Activities & Talks

  • オートファジーにおけるホスファチジルコリン (PC) 供給機構の解析  [Not invited]
    小笠原 裕太
    第123回日本解剖学会総会  2018/03
  • オートファゴソームへの膜脂質供給機構の解析  [Not invited]
    小笠原 裕太
    2017年度生命科学系学会合同年次大会  2017/12


  • Stearoyl CoA desaturase 1活性はULK1のオートファゴソーム形成部位への転座等のオートファゴソーム形成の初期段階に必要である(Stearoyl CoA desaturase 1 activity is required for the early stage of autophagosome formation such as translocation of ULK1 to autophagosome formation site)
    小笠原 裕太, 板倉 英祐, 水島 昇, 新井 洋由, 奈良 篤樹, 水上 民夫, 山本 章嗣  日本生化学会大会プログラム・講演要旨集  86回-  2T11a  -02  2013/09  [Not refereed][Not invited]

Awards & Honors

  • 2017/05 新学術領域研究「リポクオリティ」 MIP (Most Impressive Presentation) 賞
    受賞者: 小笠原 裕太
  • 2014/06 日本細胞生物学会 若手優秀発表賞
     Stearoyl-CoA Desaturase 1の活性はオートファゴソーム形成初期過程に必要である 
    受賞者: 小笠原 裕太
  • 2013/09 日本生化学会 鈴木紘一メモリアル賞
     Stearoyl-CoA desaturase 1 activity is required for the early stage of autophagosome formation suchas translocation of ULK1 to autophagosome formation site. 
    受賞者: 小笠原 裕太

Research Grants & Projects

  • 核膜脂質代謝制御の変化に伴う核膜ストレス発生機構の解析
    日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2021/04 -2024/03 
    Author : 小笠原 裕太
  • 長時間にわたって継続するオートファジーを維持する機構の解析
    日本学術振興会:科学研究費助成事業 若手研究
    Date (from‐to) : 2019/04 -2021/03 
    Author : 小笠原 裕太
    真核生物が持つ分解系の一種オートファジーについて、生体膜の主成分であるホスファチジルコリン(PC)を合成するKennedy経路が関わる『長時間にわたって継続するオートファジーを維持する』機構を明らかにすることを目的にKennedy経路の律速酵素CTP:phosphocholine cytidylyltransferase(CCT)のアイソザイムCCTβ3に着目した解析を行った。申請者はこれまでに、マウス線維芽細胞においてCCTβ3の活性が長時間飢餓条件下におけるオートファジーの活性の維持おいて重要であることを見出していたが、今回新たに癌細胞の増殖においても重要な役割を果たす可能性を見出した。骨肉腫細胞U2OSにおいて長時間の飢餓条件下ではCCTβ3が脂肪滴へとリクルートされ、このときGFP-LC3陽性のオートファジー膜が伸長する様子がライブ観察により明らかとなった。さらにCCTβを欠損させると短時間飢餓条件下におけるオートファジー活性には影響を与えないが、長時間飢餓条件下での活性については有意に減少することを見出した。またCCTβを欠損させた腫瘍細胞の長時間飢餓時の生存率が著しく減少することも明らかとなった。さらにCCTβを欠損させた細胞にCCTβ3を入れ戻すことで欠損に伴うフェノタイプが改善されることも明らかとなった。これら点からCCTβ3がもつオートファジーにおけるユニークな機能が明らかとなった。本研究によって得られた成果は、腫瘍細胞などで見られる長期的なオートファジーに標的を絞った阻害剤の開発に寄与する知見を提供するだけでなく、これまで報告がなかった全く新しいオートファゴソームへの膜脂質供給機構の一端を明らかにした。これらの成果をまとめた論文が2020年9月にnature communicationsよりパブリッシュされた。
  • オートファジー膜形成におけるリン脂質供給機構の解析
    Date (from‐to) : 2017/04 -2019/03 
    Author : 小笠原 裕太
  • オートファジーにおける脂質不飽和化の意義
    Date (from‐to) : 2013/04 -2014/03 
    Author : 小笠原 裕太

Social Contribution

Social Contribution

Social Contribution

  • 細胞生物若手の会の設立
    Date (from-to) : 2014/09
    Role : Planner

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