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Integrated analysis for mitochondrial morphology

Research Project

Project/Area Number 23K23562
Project/Area Number (Other) 22H02296 (2022-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2022-2023)
Section一般
Review Section Basic Section 38060:Applied molecular and cellular biology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

宮本 崇史  筑波大学, 医学医療系, 助教 (50740346)

Co-Investigator(Kenkyū-buntansha) 高橋 伸一郎  東京大学, 大学院農学生命科学研究科(農学部), 教授 (00197146)
山本 雄介  国立研究開発法人国立がん研究センター, 研究所, ユニット長 (60768117)
Project Period (FY) 2022-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2025: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsミトコンドリア / ExAPC / 形態
Outline of Research at the Start

本研究では、情報因子としてミトコンドリアの『形態』が創り出す情報を『ミトコンドリア形態コード』として定義し、このコード情報がミトコンドリアの情報媒体としての性質を再編成することで、MRS経路やオルガネラコミュニケーションにどのような影響を与えるのかを、数理解析や機械学習、そしてそれを裏付ける分子生物学的手法を組み合わせて理解する。これにより、『ミトコンドリアの形態が情報因子として担っている生理学的・病理学的意義とは何か?』という本研究課題の核心をなす学術的「問い」に迫る。

Outline of Annual Research Achievements

ミトコンドリアの『形態』は様々な生理学的・病理学的事象の形成に寄与する『情報因子』の1つとして認識されつつあるが、その詳細は十分に理解されていない。そこで本研究ではまず、ミトコンドリアの『形態』が情報因子として担う役割を①『局在情報の改編』、②『反応場の改編』、③『特質の改編』に分類し、これらを『ミトコンドリア形態コード』として統合的に理解・記述することを目指す。さらにこのコード情報が、ミトコンドリアが情報媒体として中核的な役割を担うMitochondrial Retrograde Signaling Pathwayやオルガネラコミュニケーションに与える影響を、数理解析や機械学習、そしてそれを裏付ける分子生物学的手法を組み合わせて、包括的に解明することを目標とする。
2023年度は、2022年度に確立したラベルフリーイメージング技術によってミトコンドリアの形態解析を詳細に行った。その結果、ミトコンドリアの分裂と融合の過程において、ミトコンドリアが自身および他のミトコンドリアの状態を直接的・間接的に認識するメカニズムが存在する可能性を見出した。さらにミトコンドリアの膜電位を消失させた後のミトコンドリアの形態変化を観察した結果、その変化は細胞種によって異なるパターンを示すことを明らかにした。さらに同一細胞内においても、ミトコンドリアごとに応答性が異なることを見出した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

ミトコンドリアの形態コードに迫るための基盤技術が確立し、そのメカニズムを紐解くためのエビデンスを得られ始めたため。

Strategy for Future Research Activity

ミトコンドリアの分裂・融合時に、どのようにしてミトコンドリアが自身および他のミトコンドリアの状態を認識しているのか、その分子メカニズムを明らかにする。

Report

(2 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (17 results)

All 2024 2023 2022 2021

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Genetic and Functional Analyses of Patients with Marked Hypo-High-Density Lipoprotein Cholesterolemia2024

    • Author(s)
      Furuta Yasuhisa、Osaki Yoshinori、Nakagawa Yoshimi、Han Song-Iee、Araki Masaya、Shikama Akito、Ohuchi Nami、Yamazaki Daichi、Suzuki Hiroaki、Shimano Hitoshi et al.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 31 Issue: 9 Pages: 1304-1318

    • DOI

      10.5551/jat.64579

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2024-09-01
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Label-free imaging of cellular organization in living mammalian cells via external apodization phase-contrast microscopy2024

    • Author(s)
      Sari Lay Nurhana、Miyamoto Takafumi et al.
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2024.03.01.582671

    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] Activity-dependent glassy cell mechanics Ⅰ: Mechanical properties measured with active microrheology2023

    • Author(s)
      H. Ebata, K. Umeda, K. Nishizawa, W. Nagao, S. Inokuchi, Y. Sugino, T. Miyamoto, D. Mizuno
    • Journal Title

      Biophysical Journal

      Volume: In press Issue: 10 Pages: 1781-1793

    • DOI

      10.1016/j.bpj.2023.04.011

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Obesity-induced metabolic imbalance allosterically modulates CtBP2 to inhibit PPAR-alpha transcriptional activity2023

    • Author(s)
      Saito K, Sekiya M, Kainoh K, Yoshino R, Hayashi A, Han SI, Araki M, Ohno H, Takeuchi Y, Tsuyuzaki T, Yamazaki D, Wanpei C, Hada L, Watanabe S, Paramita Adi Putri PI, Murayama Y, Sugano Y, Osaki Y, Iwasaki H, Yahagi N, Suzuki H, Miyamoto T, Matsuzaka T, Shimano H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 299 Issue: 7 Pages: 104890-104890

    • DOI

      10.1016/j.jbc.2023.104890

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of CtBP2 may be a mechanistic link between metabolic derangements and progressive impairment of pancreatic β cell function2023

    • Author(s)
      Sekiya M, Ma Y, Kainoh K, Saito K, Yamazaki D, Tsuyuzaki T, Chen W, Adi Putri PIP, Ohno H, Miyamoto T, Takeuchi Y, Murayama Y, Sugano Y, Osaki Y, Iwasaki H, Yahagi N, Suzuki H, Motomura K, Matsuzaka T, Murata K, Mizuno S, Takahashi S, Shimano H.
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 8 Pages: 112914-112914

    • DOI

      10.1016/j.celrep.2023.112914

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] <scp>GR‐KLF15</scp> pathway controls hepatic lipogenesis during fasting2023

    • Author(s)
      Takeuchi Y, Murayama Y, Aita Y, Mehrazad Saber Z, Karkoutly S, Tao D, Katabami K, Ye C, Shikama A, Masuda Y, Izumida Y, Miyamoto T, Matsuzaka T, Kawakami Y, Shimano H, Yahagi N.
    • Journal Title

      The FEBS Journal

      Volume: 291 Issue: 2 Pages: 259-271

    • DOI

      10.1111/febs.16957

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-Cell Transcriptome Profiling of Pancreatic Islets From Early Diabetic Mice Identifies Anxa10 for Ca2+ Allostasis Toward β-Cell Failure2023

    • Author(s)
      Motomura K, Matsuzaka T, Shichino S, Ogawa T, Pan H, Nakajima T, Asano Y, Okayama T, Takeuchi T, Ohno H, Han SI, Miyamoto T, Takeuchi Y, Sekiya M, Sone H, Yahagi N, Nakagawa Y, Oda T, Ueha S, Ikeo K, Ogura A, Matsushima K, Shimano H.
    • Journal Title

      Diabetes

      Volume: 73 Issue: 1 Pages: 75-92

    • DOI

      10.2337/db23-0212

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rhomboid protease RHBDL4/RHBDD1 cleaves SREBP-1c at endoplasmic reticulum monitoring and regulating fatty acids2023

    • Author(s)
      Han Song-Iee、Nakakuki Masanori、Nakagawa Yoshimi、Takeda Hiroyuki、Mizunoe Yuhei、Kainoh Kenta、Murayama Yuki、Aita Yuichi、Takeuchi Yoshinori、Osaki Yoshinori、Miyamoto Takafumi、Sekiya Motohiro、Matsuzaka Takashi、Yahagi Naoya、Sone Hirohito、Daitoku Hiroaki、Sato Ryuichiro、Kawano Hiroyuki、Shimano Hitoshi
    • Journal Title

      PNAS Nexus

      Volume: 2 Issue: 11 Pages: 1-14

    • DOI

      10.1093/pnasnexus/pgad351

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction.2022

    • Author(s)
      Nakajima R, Sekiya M, Furuta Y, Miyamoto T, Sato M, Fukuda K, et, al.
    • Journal Title

      Endocrinol Diabetes Metab Case Rep.

      Volume: 22 Pages: 0368-0368

    • DOI

      10.1530/edm-22-0368

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatocyte- or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced nonalcoholic fatty liver disease.2022

    • Author(s)
      Araki M, Nakagawa Y, Saito H, Yamada Y, Han SI, Mizunoe Y, Ohno H, Miyamoto T, Sekiya M, Matsuzaka T, Sone H, Shimano H.
    • Journal Title

      Am J Physiol Gastrointest Liver Physiol

      Volume: 323 Issue: 6 Pages: 627-639

    • DOI

      10.1152/ajpgi.00090.2022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Heat shock‐induced heme oxygenase‐1 expression in a mouse hepatoma cell line is dependent on <scp>HSF1</scp> and modified by <scp>NRF2</scp> and <scp>BACH1</scp>2022

    • Author(s)
      Inouye Sachiye、Kubo Takanori、Miyamoto Takafumi、Iyoda Takuya、Okita Naoyuki、Akagi Reiko
    • Journal Title

      Genes to Cells

      Volume: 27 Issue: 12 Pages: 719-730

    • DOI

      10.1111/gtc.12986

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ELOVL5-mediated fatty acid elongation promotes cellular proliferation and invasion in renal cell carcinoma2022

    • Author(s)
      Nitta Satoshi、Kandori Shuya、Tanaka Ken、Sakka Shotaro、Siga Masanobu、Nagumo Yoshiyuki、Negoro Hiromitsu、Kojima Takahiro、Mathis Bryan J.、Shimazui Toru、Miyamoto Takafumi、Matsuzaka Takashi、Shimano Hitoshi、Nishiyama Hiroyuki
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 8 Pages: 2738-2752

    • DOI

      10.1111/cas.15454

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Morphological and functional adaptation of pancreatic islet blood vessels to insulin resistance is impaired in diabetic db/db mice2022

    • Author(s)
      Okajima Yuka、Matsuzaka Takashi、Miyazaki Shun、Motomura Kaori、Ohno Hiroshi、Sharma Rahul、Shimura Takuya、Istiqamah Nurani、Han Song-iee、Mizunoe Yuhei、Osaki Yoshinori、Iwasaki Hitoshi、Yatoh Shigeru、Suzuki Hiroaki、Sone Hirohito、Miyamoto Takafumi、Aita Yuichi、Takeuchi Yoshinori、Sekiya Motohiro、Shimano Hitoshi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1868 Issue: 4 Pages: 166339-166339

    • DOI

      10.1016/j.bbadis.2022.166339

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rapid manipulation of mitochondrial morphology in a living cell with iCMM2021

    • Author(s)
      Miyamoto Takafumi、Uosaki Hideki、Mizunoe Yuhei、Han Song-Iee、Goto Satoi、Yamanaka Daisuke、Masuda Masato、Yoneyama Yosuke、Nakamura Hideki、Hattori Naoko、Takeuchi Yoshinori、Ohno Hiroshi、Sekiya Motohiro、Matsuzaka Takashi、Hakuno Fumihiko、Takahashi Shin-Ichiro、Yahagi Naoya、Ito Koichi、Shimano Hitoshi
    • Journal Title

      Cell Reports Methods

      Volume: 1 Issue: 4 Pages: 100052-100052

    • DOI

      10.1016/j.crmeth.2021.100052

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Rapid Manipulation of Mitochondrial Morphology in a Living Cell with iCMM2023

    • Author(s)
      Takafumi Miyamoto
    • Organizer
      Gordon Research Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] イメージングメタアナリシスの現状と課題2022

    • Author(s)
      宮本崇史
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 情報因子としてのオルガネラ形態に対する理解と制御2022

    • Author(s)
      宮本崇史
    • Organizer
      第19回糖鎖科学コンソーシアムシンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited

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Published: 2022-04-19   Modified: 2024-12-25  

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