Regulatory mechanism of intracellular temperature sensing and energy metabolism

• Project Area: Integrative understanding of biological phenomena with temperature as a key theme
• Project/Area Number: 15H05930
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: UMEDA Masato 京都大学, 工学研究科, 教授 (10185069)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥103,610,000 (Direct Cost: ¥79,700,000、Indirect Cost: ¥23,910,000); Fiscal Year 2019: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2018: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2017: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2016: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000); Fiscal Year 2015: ¥29,510,000 (Direct Cost: ¥22,700,000、Indirect Cost: ¥6,810,000)
• Keywords: 生理学 / 酵素 / 脂質 / 発現制御 / 昆虫 / 体温調節 / エネルギー代謝

Outline of Final Research Achievements

The temperature inside single cells directly influences a broad range of biological processes and cellular functions. However, it remains unclear whether cells autonomously regulate their intracellular temperature against changes in the extracellular temperature. We measured the temperature intracellular temperature using two mechanistically independent intracellular thermometers. We found that the intracellular temperature is increased by about 3.0℃ in a manner dependent on Δ9-fatty acid desaturase DESAT1. The DESAT1-mediated increase of intracellular temperature was caused by the enhancement of F1Fo-ATPase-dependent mitochondrial respiration in the inner mitochondrial membrane. Cold exposure of S2 cells caused the enhanced production of unsaturated fatty acid-containing phospholipids in a DESAT1-dependent manner followed by the activation of mitochondrial respiration that is coupled with mitochondrial thermogenesis.

Academic Significance and Societal Importance of the Research Achievements

現在、地球温暖化に伴う生物種の大量絶滅、生息域の変化、感染症の拡大への対処が焦眉の課題として問われている。従来、環境温の変化が生命活動にいかなる影響を及ぼすかについての学術領域は、主に生態学や動物行動学をはじめとするマクロ生物学を軸として進められている。一方、現代の分子生物学の発展により生命活動を分子レベルで理解する基礎が築かれてきているが、生命活動に及ぼす温度の影響を分子レベルで体系的に理解する試みは未だわずかである。本研究では、細胞にも、動物と同様に、環境温の変動に応じて自律的に細胞内温度を制御する仕組みが存在すること、さらにその分子機構の一端を明らかにした点にその学術的意義がある。

Research Products

• [Journal Article] Changes in the physicochemical properties of fish cell membranes during cellular senescence (2020)
  • Author(s): Akifumi Shiomi, Kohjiro Nagao, Hisae Kasai, Yuji Hara, Masato Umeda
  • Journal Title: BIOSCIENCE, BIOTECHNOLOGY, AND BIOCHEMISTRY Volume: 84 Issue: 3 Pages: 583-593
  • DOI: 10.1080/09168451.2019.1695576
  • Peer Reviewed / Open Access
• [Journal Article] Structure and Function of Δ9-Fatty Acid Desaturase (2019)
  • Author(s): Nagao, K., Murakami, A., Umeda, M.
  • Journal Title: Chemical and Pharmaceutical Bulletin Volume: 67 Issue: 4 Pages: 327-332
  • DOI: 10.1248/cpb.c18-01001
  • NAID: 130007621738
  • ISSN: 0009-2363, 1347-5223
  • Year and Date: 2019-04-01
  • Peer Reviewed / Open Access
• [Journal Article] Different mechanisms for selective transport of fatty acids using a single class of lipoprotein in Drosophila (2019)
  • Author(s): Naoya Matsuo, Kohjiro Nagao, Takuto Suito, Naoto Juni, Utako Kato, Yuji Hara, Masato Umeda
  • Journal Title: Journal of Lipid Research Volume: 60 Issue: 7 Pages: 1199-1211
  • DOI: 10.1194/jlr.m090779
  • Peer Reviewed / Open Access
• [Journal Article] Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation (2018)
  • Author(s): Tsuchiya Masaki、Hara Yuji、Okuda Masaki、Itoh Karin、Nishioka Ryotaro、Shiomi Akifumi、Nagao Kohjiro、Mori Masayuki、Mori Yasuo、Ikenouchi Junichi、Suzuki Ryo、Tanaka Motomu、Ohwada Tomohiko、Aoki Junken、Kanagawa Motoi、Toda Tatsushi、Nagata Yosuke、Matsuda Ryoichi、Takayama Yasunori、Tominaga Makoto、Umeda Masato
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 2049-2049
  • DOI: 10.1038/s41467-018-04436-w
  • NAID: 120006471161
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transport and Metabolism of Carotenoids in Drosophila melanogaster. (2018)
  • Author(s): Suito, T., Nagao, K., Umeda, M.
  • Journal Title: Carotenoid Science Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Synthesis of omega-3 long-chain polyunsaturated fatty acid-rich triacylglycerols in an endemic goby, Gymnogobius isaza, from Lake Biwa, Japan (2018)
  • Author(s): Suito Takuto、Nagao Kohjiro、Hatano Masataka、Kohashi Kenichi、Tanabe Aiko、Ozaki Hiromichi、Kawamoto Jun、Kurihara Tatsuo、Mioka Tetsuo、Tanaka Kazuma、Hara Yuji、Umeda Masato
  • Journal Title: The Journal of Biochemistry Volume: in press Issue: 2 Pages: 127-140
  • DOI: 10.1093/jb/mvy035
  • NAID: 40021635152
  • Peer Reviewed
• [Journal Article] Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy (2018)
  • Author(s): Shimasaki K, Watanabe-Takahashi M, Umeda M, Funamoto S, Saito Y, Noguchi N, Kumagai K, Hanada K, Tsukahara F, Maru Y, Shibata N, Naito M, Nishikawa K.
  • Journal Title: Genes to Cells Volume: 23 Issue: 1 Pages: 22-34
  • DOI: 10.1111/gtc.12544
  • Peer Reviewed / Open Access
• [Journal Article] An N-terminal di-proline motif is essential for fatty acid-dependent degradation of Δ9-desaturase inDrosophila (2017)
  • Author(s): Murakami Akira、Nagao Kohjiro、Juni Naoto、Hara Yuji、Umeda Masato
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 49 Pages: 19976-19986
  • DOI: 10.1074/jbc.m117.801936
  • Peer Reviewed / Open Access
• [Journal Article] ショウジョウバエを用いた体温調節行動の解析:温度受容体と共生細菌を介した制御 (2017)
  • Author(s): 水藤拓人・長尾耕治郎・梅田眞郷
  • Journal Title: 化学と生物 Volume: 55 Pages: 803-809
  • NAID: 130007519790
  • Peer Reviewed / Open Access
• [Journal Article] 生体膜におけるリン脂質ダイナミクスとその生物機能 (2016)
  • Author(s): 土谷正樹・原雄二・梅田眞郷
  • Journal Title: 膜 Volume: 41 Pages: 196-201
  • NAID: 130005421182
• [Journal Article] ショウジョウバエのリン脂質輸送タンパク質－ユニークな形質膜のリン脂質の組成と分布 (2016)
  • Author(s): 長尾耕治郎・塩見晃史・梅田眞郷
  • Journal Title: 生体の化学 Volume: 63 Pages: 247-251
• [Journal Article] Evaluation of aegerolysins as novel tools to detect and visualize ceramide phosphoethanolamine, a major sphingolipid in invertebrates (2015)
  • Author(s): Bhat HB, Ishitsuka R, Inaba T, Murate M, Abe M, Makino A, Kohyama-Koganeya A, Nagao K, Kurahashi A, Kishimoto T, Tahara M, Yamano A, Nagamune K, Hirabayashi Y, Juni N, Umeda M, Fujimori F, Nishibori K, Yamaji-Hasegawa A, Greimel P, Kobayashi T.
  • Journal Title: FASEB J Volume: 29(9) Issue: 9 Pages: 3920-34
  • DOI: 10.1096/fj.15-272112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 脂質ダイナミズムから生命現象を理解する (2020)
  • Author(s): 梅田眞郷
  • Organizer: リポクオリティ領域会議
  • Invited
• [Presentation] 脂質改変による冬眠の誘導 (2019)
  • Author(s): 梅田眞郷、原雄二、長尾耕治郎
  • Organizer: 理化学研究所BDR人工冬眠に向けての勉強会
  • Invited
• [Presentation] 膜脂質を介する細胞内温度制御の分子機構 (2019)
  • Author(s): 梅田眞郷、村上光、長尾耕治郎
  • Organizer: 第71回日本細胞生物学会シンポジウム
  • Invited
• [Presentation] 脂質の分子運動から生命現象を探る (2019)
  • Author(s): 梅田眞郷
  • Organizer: 生化学若い研究者の会
  • Invited
• [Presentation] 膜脂質を介する細胞内温度の制御機構 (2019)
  • Author(s): 梅田眞郷、村上光、長尾耕治郎
  • Organizer: 第57回日本生物物理学会年会シンポジウム
  • Invited
• [Presentation] 昆虫から学ぶ骨格筋細胞の膜と代謝 (2019)
  • Author(s): 梅田眞郷
  • Organizer: 第7回若手骨格筋研究会
  • Invited
• [Presentation] 生体膜の分子機構 (2019)
  • Author(s): 梅田眞郷
  • Organizer: 兵庫医科大学特別講演
  • Invited
• [Presentation] 生物と温度 (2019)
  • Author(s): 梅田眞郷
  • Organizer: 和敬論談会
  • Invited
• [Presentation] Organization and deformability of insect cell membrane. (2019)
  • Author(s): Masato Umeda
  • Organizer: The 16th International Membrane Research Forum
  • Int'l Joint Research / Invited
• [Presentation] 脂質ダイナミクスの生物機能 (2018)
  • Author(s): 梅田眞郷
  • Organizer: 第13回スフィンゴテラピィ研究会
  • Invited
• [Presentation] Phospholipid flippase acts as a molecular switch for ion channel activation. (2018)
  • Author(s): Masato Umeda
  • Organizer: Membrane Lipid Transporter Symposium 2018-Flippases, Floppases and Scramblases
  • Int'l Joint Research / Invited
• [Presentation] Phospholipid flip-flop as a molecular switch for ion channel activation. (2018)
  • Author(s): Masato Umeda
  • Organizer: 2nd Japan-Korea Lipid Joint Symposium
  • Int'l Joint Research / Invited
• [Presentation] Phospholipid flip-flop as a molecular switch for ion channel activation. (2018)
  • Author(s): Masato Umeda
  • Organizer: The 23rd International Symposium on Plant Lipids
  • Int'l Joint Research / Invited
• [Presentation] 膜リン脂質のフリップフロップ・スイッチによるイオンチャネルの制御 (2017)
  • Author(s): 梅田眞郷
  • Organizer: 老化過程における細胞膜のリン脂質非対称性の生理機能と病態に関するセミナー
  • Invited
• [Presentation] 昆虫から学ぶ (2017)
  • Author(s): 梅田眞郷
  • Organizer: 新潟薬科大学薬学総合セミナー
  • Invited
• [Presentation] 昆虫から学ぶ脂質の機能と代謝 (2017)
  • Author(s): 梅田眞郷
  • Organizer: 第31回カロテノイド研究談話会
  • Invited
• [Presentation] Remarkable deformability of insect cell is supported by constitutively active phospholipid scramblase. (2017)
  • Author(s): Masato Umeda, Akifumi Shiomi, Kohjiro Nagao
  • Organizer: Molecular & Cellular Biology of Gordon Research Conference
  • Int'l Joint Research
• [Presentation] Dietary response governing thermoregulatory behavior (2016)
  • Author(s): Masato Umeda, Takuto Suito, Naoto Juni, Kojiro Nagao
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(横浜）
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] 腸内細菌を介する行動性体温調節の分子機構 (2016)
  • Author(s): 梅田眞郷、水藤拓人、従二直人、長尾耕治郎
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（仙台）
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] 体温はいかにして決まるのか？ (2016)
  • Author(s): 梅田眞郷
  • Organizer: HiHA第7回Workshop
  • Place of Presentation: 広島大学(広島）
  • Year and Date: 2016-09-23
  • Invited
• [Presentation] 温度センシングとエネルギー代謝 (2016)
  • Author(s): 梅田眞郷
  • Organizer: 第68回日本細胞生化学会大会
  • Place of Presentation: 京都テルサ(京都）
  • Year and Date: 2016-06-15
  • Invited
• [Presentation] 膜脂質ダイナミクスを介する細胞機能の制御機構 (2016)
  • Author(s): 梅田真郷
  • Organizer: 日本膜学会「第38年会」
  • Place of Presentation: 早稲田大学西早稲田キャンパス(東京）
  • Year and Date: 2016-05-10
  • Invited
• [Presentation] 膜脂質ダイナミクスを介する細胞機能の制御機構 (2016)
  • Author(s): 梅田真郷
  • Organizer: 日本膜学会「第38年会」
  • Place of Presentation: 早稲田大学(東京）
  • Year and Date: 2016-05-10
  • Invited
• [Presentation] 質を介するエネルギー代謝と温度調節行動の制御機構 (2016)
  • Author(s): 梅田真郷
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター(札幌）
  • Year and Date: 2016-03-24
  • Invited
• [Presentation] 生体膜脂質と温度感受性システム (2016)
  • Author(s): 梅田真郷
  • Organizer: 第36回白金シンポジウム
  • Place of Presentation: 北里大学薬学部(東京）
  • Year and Date: 2016-02-27
  • Invited
• [Presentation] 生体膜におけるリン脂質分子の運動と機能 (2015)
  • Author(s): 梅田真郷
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 金沢大学(金沢）
  • Year and Date: 2015-09-13
  • Invited
• [Presentation] 呼吸とエネルギー代謝：昆虫の秘密から学ぶ (2015)
  • Author(s): 梅田真郷
  • Organizer: 第19回酵素ダイナミクス研究会
  • Place of Presentation: 東京女子医科大学(東京）
  • Year and Date: 2015-09-12
  • Invited
• [Presentation] symmetric transbilayer distribution of membrane phospholipids is disrupted by constitutive activation of phospholipid scramblase in insect cells. (2015)
  • Author(s): Masato Umeda
  • Organizer: Lipids, Molecular & Cellular Biology of Gordon Research Conference
  • Place of Presentation: Waterville Valley（USA）
  • Year and Date: 2015-07-26
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] エイコサンペンタエン酸を生産する微生物 (2020)
  • Inventor(s): 梅田 眞郷, 従二 直人, 長尾 耕治郎
  • Industrial Property Rights Holder: 国立大学法人京都大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-123809
  • Filing Date: 2020