Updated on 2024/09/25

Information

 

写真a

 
KANKI TOMOTAKE
 
Organization
Faculty of Medical Sciences Department of Basic Medicine Professor
School of Medicine Department of Medicine(Concurrent)
Graduate School of Medical Sciences Department of Medicine(Concurrent)
Graduate School of Medical Sciences Department of Medical Sciences(Concurrent)
Title
Professor
Contact information
メールアドレス
Tel
0926426085
Profile
ミトコンドリア恒常性に関する研究とその成果を利用したミトコンドリア関連疾患の治療法開発。特に、ミトコンドリアオートファジー(マイトファジー)やミトコンドリア形態、ミトコンドリアDNAに着目し研究開発を進めている。
External link

Degree

  • MD., Ph.D.

Research History

  • 新潟大学大学院医歯学総合研究科

Research Interests・Research Keywords

  • Research theme:Mitochondrial homeostasis

    Keyword:Mitophagy, Mitochondrial morphology, Mitochondrial DNA

    Research period: 2024.4

Awards

  • 文部科学大臣表彰若手科学者賞

    2012.4   文部科学省  

Papers

  • Comprehensive analysis of non-selective and selective autophagy in yeast <i>atg</i> mutants and characterization of autophagic activity in the absence of the Atg8 conjugation system Reviewed International journal

    Tamara Ginevskaia, Aleksei Innokentev, Kentaro Furukawa, Tomoyuki Fukuda, Manabu Hayatsu, Shun-ichi Yamashita, Keiichi Inoue, Shinsuke Shibata, Tomotake Kanki

    The Journal of Biochemistry   176 ( 3 )   217 - 227   2024.6   ISSN:0021-924X eISSN:1756-2651

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    Abstract

    Most autophagy-related genes, or ATG genes, have been identified in studies using budding yeast. Although the functions of the ATG genes are well understood, the contributions of individual genes to non-selective and various types of selective autophagy remain to be fully elucidated. In this study, we quantified the activity of non-selective autophagy, the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy, endoplasmic reticulum (ER)-phagy, and pexophagy in all Saccharomyces cerevisiae atg mutants. Among the mutants of the core autophagy genes considered essential for autophagy, the atg13 mutant and mutants of the genes involved in the two ubiquitin-like conjugation systems retained residual autophagic functionality. In particular, mutants of the Atg8 ubiquitin-like conjugation system (the Atg8 system) exhibited substantial levels of non-selective autophagy, the Cvt pathway, and pexophagy, although mitophagy and ER-phagy were undetectable. Atg8-system mutants also displayed intravacuolar vesicles resembling autophagic bodies, albeit at significantly reduced size and frequency. Thus, our data suggest that membranous sequestration and vacuolar delivery of autophagic cargo can occur in the absence of the Atg8 system. Alongside these findings, the comprehensive analysis conducted here provides valuable datasets for future autophagy research.

    DOI: 10.1093/jb/mvae042

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  • Atg44/Mdi1/mitofissin facilitates Dnm1-mediated mitochondrial fission Reviewed International journal

    Kentaro Furukawa, Manabu Hayatsu, Kentaro Okuyama, Tomoyuki Fukuda, Shun-Ichi Yamashita, Keiichi Inoue, Shinsuke Shibata, Tomotake Kanki

    Autophagy   1 - 9   2024.6   ISSN:1554-8627 eISSN:1554-8635

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Informa UK Limited  

    DOI: 10.1080/15548627.2024.2360345

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  • Re-exploration of all <i>ATG</i> genes

    Kentaro Furukawa, Tamara Ginevskaia, Tomotake Kanki

    Autophagy Reports   3 ( 1 )   2024.8   eISSN:2769-4127

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    Publishing type:Research paper (scientific journal)   Publisher:Informa UK Limited  

    DOI: 10.1080/27694127.2024.2386194

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  • Identification and characterization of mitophagy proteins promoting mitochondrial degradation

    Fukuda Tomoyuki, Kanki Tomotake

    96 ( 3 )   394 - 398   2024.6   ISSN:00371017

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    Authorship:Last author, Corresponding author   Language:Japanese  

    DOI: 10.14952/seikagaku.2024.960394

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  • Imeglimin mitigates the accumulation of dysfunctional mitochondria to restore insulin secretion and suppress apoptosis of pancreatic β-cells from db/db mice International journal

    Kyota Aoyagi, Chiyono Nishiwaki, Yoko Nakamichi, Shun-ichi Yamashita, Tomotake Kanki, Mica Ohara-Imaizumi

    Scientific Reports   14 ( 1 )   2024.3   eISSN:2045-2322

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    Abstract

    Mitochondrial dysfunction in pancreatic β-cells leads to impaired glucose-stimulated insulin secretion (GSIS) and type 2 diabetes (T2D), highlighting the importance of autophagic elimination of dysfunctional mitochondria (mitophagy) in mitochondrial quality control (mQC). Imeglimin, a new oral anti-diabetic drug that improves hyperglycemia and GSIS, may enhance mitochondrial activity. However, chronic imeglimin treatment’s effects on mQC in diabetic β-cells are unknown. Here, we compared imeglimin, structurally similar anti-diabetic drug metformin, and insulin for their effects on clearance of dysfunctional mitochondria through mitophagy in pancreatic β-cells from diabetic model db/db mice and mitophagy reporter (CMMR) mice. Pancreatic islets from db/db mice showed aberrant accumulation of dysfunctional mitochondria and excessive production of reactive oxygen species (ROS) along with markedly elevated mitophagy, suggesting that the generation of dysfunctional mitochondria overwhelmed the mitophagic capacity in db/db β-cells. Treatment with imeglimin or insulin, but not metformin, reduced ROS production and the numbers of dysfunctional mitochondria, and normalized mitophagic activity in db/db β-cells. Concomitantly, imeglimin and insulin, but not metformin, restored the secreted insulin level and reduced β-cell apoptosis in db/db mice. In conclusion, imeglimin mitigated accumulation of dysfunctional mitochondria through mitophagy in diabetic mice, and may contribute to preserving β-cell function and effective glycemic control in T2D.

    DOI: 10.1038/s41598-024-56769-w

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    Other Link: https://www.nature.com/articles/s41598-024-56769-w

  • Mitophagy mediated by BNIP3 and NIX protects against ferroptosis by downregulating mitochondrial reactive oxygen species. Reviewed International coauthorship International journal

    Shun-Ichi Yamashita, Yuki Sugiura, Yuta Matsuoka, Rae Maeda, Keiichi Inoue, Kentaro Furukawa, Tomoyuki Fukuda, David C Chan, Tomotake Kanki

    Cell death and differentiation   2024.3

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    Mitophagy plays an important role in the maintenance of mitochondrial homeostasis and can be categorized into two types: ubiquitin-mediated and receptor-mediated pathways. During receptor-mediated mitophagy, mitophagy receptors facilitate mitophagy by tethering the isolation membrane to mitochondria. Although at least five outer mitochondrial membrane proteins have been identified as mitophagy receptors, their individual contribution and interrelationship remain unclear. Here, we show that HeLa cells lacking BNIP3 and NIX, two of the five receptors, exhibit a complete loss of mitophagy in various conditions. Conversely, cells deficient in the other three receptors show normal mitophagy. Using BNIP3/NIX double knockout (DKO) cells as a model, we reveal that mitophagy deficiency elevates mitochondrial reactive oxygen species (mtROS), which leads to activation of the Nrf2 antioxidant pathway. Notably, BNIP3/NIX DKO cells are highly sensitive to ferroptosis when Nrf2-driven antioxidant enzymes are compromised. Moreover, the sensitivity of BNIP3/NIX DKO cells is fully rescued upon the introduction of wild-type BNIP3 and NIX, but not the mutant forms incapable of facilitating mitophagy. Consequently, our results demonstrate that BNIP3 and NIX-mediated mitophagy plays a role in regulating mtROS levels and protects cells from ferroptosis.

    DOI: 10.1038/s41418-024-01280-y

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  • Mitophagy Responds to the Environmental Temperature and Regulates Mitochondrial Mass in Adipose Tissues.

    Yamashita SI, Kanki T

    Advances in experimental medicine and biology   1461   229 - 243   2024   ISSN:0065-2598

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    DOI: 10.1007/978-981-97-4584-5_16

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  • Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis. Reviewed International journal

    Yen Teng Tai, Tomoyuki Fukuda, Yuichi Morozumi, Hayato Hirai, Arisa H Oda, Yoshiaki Kamada, Yutaka Akikusa, Tomotake Kanki, Kunihiro Ohta, Kazuhiro Shiozaki

    Molecular and cellular biology   1 - 18   2023.12

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    Target of rapamycin complex 1 (TORC1) is activated in response to nutrient availability and growth factors, promoting cellular anabolism and proliferation. To explore the mechanism of TORC1-mediated proliferation control, we performed a genetic screen in fission yeast and identified Sfp1, a zinc-finger transcription factor, as a multicopy suppressor of temperature-sensitive TORC1 mutants. Our observations suggest that TORC1 phosphorylates Sfp1 and protects Sfp1 from proteasomal degradation. Transcription analysis revealed that Sfp1 positively regulates genes involved in ribosome production together with two additional transcription factors, Ifh1/Crf1 and Fhl1. Ifh1 physically interacts with Fhl1, and the nuclear localization of Ifh1 is regulated in response to nutrient levels in a manner dependent on TORC1 and Sfp1. Taken together, our data suggest that the transcriptional regulation of the genes involved in ribosome biosynthesis by Sfp1, Ifh1, and Fhl1 is one of the key pathways through which nutrient-activated TORC1 promotes cell proliferation.

    DOI: 10.1080/10985549.2023.2282349

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  • Mitofissin: a novel mitochondrial fission protein that facilitates mitophagy. International journal

    Tomoyuki Fukuda, Kentaro Furukawa, Tatsuro Maruyama, Nobuo N Noda, Tomotake Kanki

    Autophagy   19 ( 11 )   3019 - 3021   2023.11

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    Atg: autophagy related; IMM: inner mitochondrial membrane; IMS: intermembrane space; PAS: phagophore assembly site; SAR: selective autophagy receptor.

    DOI: 10.1080/15548627.2023.2237343

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  • Neuronal MML-1/MXL-2 regulates systemic aging via glutamate transporter and cell nonautonomous autophagic and peroxidase activity. Reviewed International journal

    Tatsuya Shioda, Ittetsu Takahashi, Kensuke Ikenaka, Naonobu Fujita, Tomotake Kanki, Toshihiko Oka, Hideki Mochizuki, Adam Antebi, Tamotsu Yoshimori, Shuhei Nakamura

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 39 )   e2221553120   2023.9

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    Accumulating evidence has demonstrated the presence of intertissue-communication regulating systemic aging, but the underlying molecular network has not been fully explored. We and others previously showed that two basic helix-loop-helix transcription factors, MML-1 and HLH-30, are required for lifespan extension in several longevity paradigms, including germlineless Caenorhabditis elegans. However, it is unknown what tissues these factors target to promote longevity. Here, using tissue-specific knockdown experiments, we found that MML-1 and its heterodimer partners MXL-2 and HLH-30 act primarily in neurons to extend longevity in germlineless animals. Interestingly, however, the downstream cascades of MML-1 in neurons were distinct from those of HLH-30. Neuronal RNA interference (RNAi)-based transcriptome analysis revealed that the glutamate transporter GLT-5 is a downstream target of MML-1 but not HLH-30. Furthermore, the MML-1-GTL-5 axis in neurons is critical to prevent an age-dependent collapse of proteostasis and increased oxidative stress through autophagy and peroxidase MLT-7, respectively, in long-lived animals. Collectively, our study revealed that systemic aging is regulated by a molecular network involving neuronal MML-1 function in both neural and peripheral tissues.

    DOI: 10.1073/pnas.2221553120

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  • Meet the authors: Tomoyuki Fukuda, Kentaro Furukawa, and Tomotake Kanki Invited International journal

    Sonhita Chakraborty, Tomoyuki Fukuda, Kentaro Furukawa, Tomotake Kanki

    Molecular Cell   83 ( 12 )   1953 - 1955   2023.6   ISSN:1097-2765

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    DOI: 10.1016/j.molcel.2023.05.016

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  • 転写因子MML-1/MXL-2による組織間コミュニケーションを介した寿命制御機構の解明

    塩田 達也, 池中 健介, 神吉 智丈, 岡 敏彦, 望月 秀樹, Antebi Adam, 吉森 保, 中村 修平

    基礎老化研究   47 ( 2 )   85 - 85   2023.6   ISSN:0912-8921

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    Language:Japanese   Publisher:日本基礎老化学会  

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  • The mitochondrial intermembrane space protein mitofissin drives mitochondrial fission required for mitophagy Reviewed International coauthorship International journal

    Tomoyuki Fukuda, Kentaro Furukawa, Tatsuro Maruyama, Shun-ichi Yamashita, Daisuke Noshiro, Chihong Song, Yuta Ogasawara, Kentaro Okuyama, Jahangir Md Alam, Manabu Hayatsu, Tetsu Saigusa, Keiichi Inoue, Kazuho Ikeda, Akira Takai, Lin Chen, Vikramjit Lahiri, Yasushi Okada, Shinsuke Shibata, Kazuyoshi Murata, Daniel J. Klionsky, Nobuo N. Noda, Tomotake Kanki

    Molecular Cell   83 ( 12 )   2045 - 2058.e9   2023.5   ISSN:1097-2765

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    DOI: 10.1016/j.molcel.2023.04.022

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  • TIM23 facilitates PINK1 activation by safeguarding against OMA1-mediated degradation in damaged mitochondria Reviewed International journal

    Shiori Akabane, Kiyona Watanabe, Hidetaka Kosako, Shun-ichi Yamashita, Kohei Nishino, Masahiro Kato, Shiori Sekine, Tomotake Kanki, Noriyuki Matsuda, Toshiya Endo, Toshihiko Oka

    Cell Reports   112454 - 112454   2023.5   ISSN:2211-1247

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    DOI: 10.1016/j.celrep.2023.112454

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  • Hva22, a REEP family protein in fission yeast, promotes reticulophagy in collaboration with a receptor protein. Reviewed International journal

    Fukuda T, Saigusa T, Furukawa K, Inoue K, Yamashita SI, Kanki T

    Autophagy.   2023.5

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    DOI: 10.1080/15548627.2023.2214029

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  • Myeloid-associated differentiation marker is an essential host factor for human parechovirus PeV-A3 entry Reviewed International journal

    Kanako Watanabe, Tomoichiro Oka, Hirotaka Takagi, Sergei Anisimov, Shun-ichi Yamashita, Yoshinori Katsuragi, Masahiko Takahashi, Masaya Higuchi, Tomotake Kanki, Akihiko Saitoh, Masahiro Fujii

    Nature Communications   14 ( 1 )   2023.3   eISSN:2041-1723

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    Abstract

    Human parechovirus (PeV-A) is an RNA virus that belongs to the family Picornaviridae and it is currently classified into 19 genotypes. PeV-As usually cause mild illness in children and adults. Among the genotypes, PeV-A3 can cause severe diseases in neonates and young infants, resulting in neurological sequelae and death. In this study, we identify the human myeloid-associated differentiation marker (MYADM) as an essential host factor for the entry of six PeV-As (PeV-A1 to PeV-A6), including PeV-A3. The infection of six PeV-As (PeV-A1 to PeV-A6) to human cells is abolished by knocking out the expression of MYADM. Hamster BHK-21 cells are resistant to PeV-A infection, but the expression of human MYADM in BHK-21 confers PeV-A infection and viral production. Furthermore, VP0 capsid protein of PeV-A3 interacts with one extracellular domain of human MYADM on the cell membrane of BHK-21. The identification of MYADM as an essential entry factor for PeV-As infection is expected to advance our understanding of the pathogenesis of PeV-As.

    DOI: 10.1038/s41467-023-37399-8

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    Other Link: https://www.nature.com/articles/s41467-023-37399-8

  • A new beta cell-specific mitophagy reporter mouse shows that metabolic stress leads to accumulation of dysfunctional mitochondria despite increased mitophagy Reviewed International journal

    Kyota Aoyagi, Shun-ichi Yamashita, Yoshihiro Akimoto, Chiyono Nishiwaki, Yoko Nakamichi, Haruhide Udagawa, Manabu Abe, Kenji Sakimura, Tomotake Kanki, Mica Ohara-Imaizumi

    Diabetologia   66 ( 1 )   147 - 162   2022.10   ISSN:0012-186X eISSN:1432-0428

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    DOI: 10.1007/s00125-022-05800-8

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    Other Link: https://link.springer.com/article/10.1007/s00125-022-05800-8/fulltext.html

  • 新潟大学における研究リスク管理 病原体等の適正管理のための取り組み

    三浦 詩織, 深見 克哉, 相馬 恵, 野水 和美, 中山 亮, 笹岡 俊邦, 神吉 智丈, 松本 壮吉, 末吉 邦

    新潟医学会雑誌   136 ( 4 )   117 - 126   2022.4   ISSN:0029-0440

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    【緒言】病原体等を取り扱う機関においては,バイオセーフティおよびバイオセキュリティの観点からそれらの保管や取扱いの管理体制を整備する責任がある.バイオリスク管理の概念は研究者の間に浸透しているものの,実際の管理運用体制は必ずしも十分に整備されていない.本研究の目的は,新潟大学のライフサイエンス研究に関連するバイオリスクを把握し,それらを包括的に管理するトータルリスクマネジメント体制の構築を促進することである.【対象と方法】始めに新潟大学における病原体等使用の現状把握を行った.全学の教職員に対し,使用している病原体等の種類や管理方法,関連法令の理解度について,アンケート調査を行った.実情に即した病原体等の管理を運用するため,それぞれの病原体等の管理基準となる学内バイオセーフティーレベル(Bio Safety Level;BSL)を定めたほか,病原体等ごとの法的規制の情報をBSL一覧表に集約化した.また,実験室における設備要件や取扱い方法の基準を定め,実験室の評価とモニタリングのための包括的な実験室要件のチェックシートを作成した.さらに法令遵守および適正管理のため,オンライン管理システムの構築を行った.【結果】新潟大学において使用されている病原体等の種類は,細菌,ウイルス,真菌,毒素,プリオンであり,寄生虫の保有はなかった.研究者により病原体等を取り扱う管理基準が統一されていないほか,病原体等を使用する実験室要件の基準の不統一が明らかになった.また,病原体等の取扱いに関する法令への理解度が低いことが明らかになった.これらの研究リスクに対応するため,病原体等の取扱基準として学内BSLを整備したほか,病原体等を用いる実験室の設備要件・取扱い要件を示した実験室チェックシートを作成した.さらに,法令規制を明確にするために,病原体等ごとの法的規制を一覧化した.関連法令や学内規程の遵守を包括的に管理するために,オンラインの研究リスク管理システムを構築した.【結論】本取り組みにより,新潟大学における病原体等使用実験を行う際に対処すべきバイオリスクおよび法令リスクが明らかとなった.それらの研究リスクへ対応するための具体的方法が明確化され,行動規範や関連法令の遵守を適正管理するための円滑なトータルリスクマネジメント体制が整備された.本成果は,今後,高度化・複雑化していくと考えられる研究コンプライアンスへ対応するための組織づくりの基盤となる.(著者抄録)

  • Mitophagy in Yeast: Molecular Mechanism and Regulation Reviewed

    Aleksei Innokentev, Tomotake Kanki

    Cells   10 ( 12 )   3569 - 3569   2021.12

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    DOI: 10.3390/cells10123569

  • Fis1 ablation in the male germline disrupts mitochondrial morphology and mitophagy, and arrests spermatid maturation. Reviewed International journal

    Grigor Varuzhanyan, Mark S Ladinsky, Shun-Ichi Yamashita, Manabu Abe, Kenji Sakimura, Tomotake Kanki, David C Chan

    Development (Cambridge, England)   148 ( 16 )   2021.8

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    DOI: 10.1242/dev.199686

  • Membrane perturbation by lipidated Atg8 underlies autophagosome biogenesis. Reviewed International journal

    Tatsuro Maruyama, Jahangir Md Alam, Tomoyuki Fukuda, Shun Kageyama, Hiromi Kirisako, Yuki Ishii, Ichio Shimada, Yoshinori Ohsumi, Masaaki Komatsu, Tomotake Kanki, Hitoshi Nakatogawa, Nobuo N Noda

    Nature structural & molecular biology   28 ( 7 )   583 - 593   2021.7

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    DOI: 10.1038/s41594-021-00614-5

  • The optineurin/TIA1 pathway inhibits aberrant stress granule formation and reduces ubiquitinated TDP-43. Reviewed International journal

    Taichi Kakihana, Masahiko Takahashi, Yoshinori Katsuragi, Shun-Ichi Yamashita, Junya Sango, Tomotake Kanki, Osamu Onodera, Masahiro Fujii

    iScience   24 ( 7 )   102733 - 102733   2021.7

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    DOI: 10.1016/j.isci.2021.102733

  • Mitophagy reporter mouse analysis reveals increased mitophagy activity in disuse-induced muscle atrophy. Reviewed International journal

    Shun-Ichi Yamashita, Masanao Kyuuma, Keiichi Inoue, Yuki Hata, Ryu Kawada, Masaki Yamabi, Yasuyuki Fujii, Junko Sakagami, Tomoyuki Fukuda, Kentaro Furukawa, Satoshi Tsukamoto, Tomotake Kanki

    Journal of cellular physiology   2021.5

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    DOI: 10.1002/jcp.30404

  • Mitophagy regulation mediated by the Far complex in yeast. International journal

    Kentaro Furukawa, Aleksei Innokentev, Tomotake Kanki

    Autophagy   17 ( 4 )   1042 - 1043   2021.4

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    DOI: 10.1080/15548627.2021.1885184

  • Atg43, a novel autophagy-related protein, serves as a mitophagy receptor to bridge mitochondria with phagophores in fission yeast. International journal

    Tomoyuki Fukuda, Tomotake Kanki

    Autophagy   17 ( 3 )   826 - 827   2021.3

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    DOI: 10.1080/15548627.2021.1874662

  • MITOL promotes cell survival by degrading Parkin during mitophagy. Reviewed International journal

    Isshin Shiiba, Keisuke Takeda, Shun Nagashima, Naoki Ito, Takeshi Tokuyama, Shun-Ichi Yamashita, Tomotake Kanki, Toru Komatsu, Yasuteru Urano, Yuuta Fujikawa, Ryoko Inatome, Shigeru Yanagi

    EMBO reports   22 ( 3 )   e49097   2021.3

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    DOI: 10.15252/embr.201949097

  • Tripartite suppression of fission yeast TORC1 signaling by the GATOR1-Sea3 complex, the TSC complex, and Gcn2 kinase. Reviewed International journal

    Tomoyuki Fukuda, Fajar Sofyantoro, Yen Teng Tai, Kim Hou Chia, Takato Matsuda, Takaaki Murase, Yuichi Morozumi, Hisashi Tatebe, Tomotake Kanki, Kazuhiro Shiozaki

    eLife   10   2021.2

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    DOI: 10.7554/eLife.60969

  • Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy. Reviewed International journal

    Aleksei Innokentev, Kentaro Furukawa, Tomoyuki Fukuda, Tetsu Saigusa, Keiichi Inoue, Shun-Ichi Yamashita, Tomotake Kanki

    eLife   9   2020.12

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    DOI: 10.7554/eLife.63694

  • Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast. Reviewed International journal

    Tomoyuki Fukuda, Yuki Ebi, Tetsu Saigusa, Kentaro Furukawa, Shun-Ichi Yamashita, Keiichi Inoue, Daiki Kobayashi, Yutaka Yoshida, Tomotake Kanki

    eLife   9   2020.11

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    DOI: 10.7554/eLife.61245

  • FKBP8 LIRL-dependent mitochondrial fragmentation facilitates mitophagy under stress conditions. Reviewed International journal

    Seung-Min Yoo, Shun-Ichi Yamashita, Hyunjoo Kim, DoHyeong Na, Haneul Lee, Seo Jin Kim, Dong-Hyung Cho, Tomotake Kanki, Yong-Keun Jung

    FASEB journal   34 ( 2 )   2944 - 2957   2020.2

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    DOI: 10.1096/fj.201901735R

  • Gemcitabine induces Parkin-independent mitophagy through mitochondrial-resident E3 ligase MUL1-mediated stabilization of PINK1. Reviewed International journal

    Ryoko Igarashi, Shun-Ichi Yamashita, Tomohiro Yamashita, Keiichi Inoue, Tomoyuki Fukuda, Takeo Fukuchi, Tomotake Kanki

    Scientific reports   10 ( 1 )   1465 - 1465   2020.1

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    DOI: 10.1038/s41598-020-58315-w

  • Glaucoma-Associated Mutations in the Optineurin Gene Have Limited Impact on Parkin-Dependent Mitophagy. Reviewed

    Chernyshova K, Inoue K, Yamashita SI, Fukuchi T, Kanki T

    Investigative ophthalmology & visual science   60 ( 10 )   3625 - 3635   2019.8

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    Glaucoma-Associated Mutations in the Optineurin Gene Have Limited Impact on Parkin-Dependent Mitophagy.

    DOI: 10.1167/iovs.19-27184

  • The PP2A-like Protein Phosphatase Ppg1 and the Far Complex Cooperatively Counteract CK2-Mediated Phosphorylation of Atg32 to Inhibit Mitophagy Reviewed

    Kentaro Furukawa, Tomoyuki Fukuda, Shun-ichi Yamashita, Tetsu Saigusa, Yusuke Kurihara, Yutaka Yoshida, Hiromi Kirisako, Hitoshi Nakatogawa, Tomotake Kanki

    Cell Reports   23 ( 12 )   3579 - 3590   2018.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.celrep.2018.05.064

  • Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeast Reviewed

    Akihiro Kondo, Md. Golam Mostofa, Katsuya Miyake, Mashu Terasawa, Islam Nafisa, Akter M.S.T. Yeasmin, Talukdar Muhammad Waliullah, Tomotake Kanki, Takashi Ushimaru

    Journal of Molecular Biology   430 ( 11 )   1671 - 1684   2018.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.jmb.2018.04.007

  • Mechanisms and Physiological Roles of Mitophagy in Yeast. Reviewed

    Fukuda T, Kanki T

    Molecules and cells   41 ( 1 )   35 - 44   2018.1

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    Mechanisms and Physiological Roles of Mitophagy in Yeast.

    DOI: 10.14348/molcells.2018.2214

  • Parkin非依存的マイトファジーにおけるPINK1の機能解析

    五十嵐 遼子, 山下 俊一, クセニヤ・チェルニショワ, 福地 健郎, 神吉 智丈

    眼科臨床紀要   10 ( 8 )   692 - 692   2017.8

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  • 正常眼圧緑内障を発症させるオプチニューリン遺伝子変異とミトコンドリア分解の関係

    クセニヤ・チェルヌショワ, 山下 俊一, 五十嵐 遼子, 福地 健郎, 神吉 智丈

    眼科臨床紀要   10 ( 8 )   691 - 692   2017.8

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    Language:Japanese  

  • Detection of Hypoxia-Induced and Iron Depletion-Induced Mitophagy in Mammalian Cells. Reviewed

    Yamashita SI, Kanki T

    Methods in molecular biology (Clifton, N.J.)   2017.3

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    Detection of Hypoxia-Induced and Iron Depletion-Induced Mitophagy in Mammalian Cells.

    DOI: 10.1007/7651_2017_19

  • Mitophagy in Yeast: A Screen of Mitophagy-Deficient Mutants. Reviewed

    Furukawa K, Kanki T

    Methods in molecular biology (Clifton, N.J.)   2017.3

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    Mitophagy in Yeast: A Screen of Mitophagy-Deficient Mutants.

    DOI: 10.1007/7651_2017_13

  • Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy Reviewed

    Shun-ichi Yamashita, Xiulian Jin, Kentaro Furukawa, Maho Hamasaki, Akiko Nezu, Hidenori Otera, Tetsu Saigusa, Tamotsu Yoshimori, Yasuyoshi Sakai, Katsuyoshi Mihara, Tomotake Kanki

    JOURNAL OF CELL BIOLOGY   215 ( 5 )   649 - 665   2016.12

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    DOI: 10.1083/jcb.201605093

  • Constitutive Activation of PINK1 Protein Leads to Proteasome-mediated and Non-apoptotic Cell Death Independently of Mitochondrial Autophagy Reviewed

    Shiori Akabane, Kohei Matsuzaki, Shun-ichi Yamashita, Kana Arai, Kei Okatsu, Tomotake Kanki, Noriyuki Matsuda, Toshihiko Oka

    JOURNAL OF BIOLOGICAL CHEMISTRY   291 ( 31 )   16162 - 16174   2016.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1074/jbc.M116.714923

  • Mitophagy in yeast: Molecular mechanisms and physiological role. Reviewed

    Kanki T, Furukawa K, Yamashita S

    Biochimica et biophysica acta   1853 ( 10 Pt B )   2756 - 2765   2015.10

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    Mitophagy in yeast: Molecular mechanisms and physiological role.

    DOI: 10.1016/j.bbamcr.2015.01.005

  • Mitophagy is primarily due to alternative autophagy and requires the MAPK1 and MAPK14 signaling pathways Reviewed

    Yuko Hirota, Shun-ichi Yamashita, Yusuke Kurihara, Xiulian Jin, Masamune Aihara, Tetsu Saigusa, Dongchon Kang, Tomotake Kanki

    AUTOPHAGY   11 ( 2 )   332 - 343   2015.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/15548627.2015.1023047

  • Atg32 Confers Selective Mitochondrial Sequestration as a Cargo for Autophagy Reviewed

    Yusuke Kurihara, Tomotake Kanki

    Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging   4   163 - 173   2014.7

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    DOI: 10.1016/B978-0-12-405528-5.00010-9

  • Tor and the Sin3-Rpd3 complex regulate expression of the mitophagy receptor protein Atg32 in yeast Reviewed

    Masamune Aihara, Xiulian Jin, Yusuke Kurihara, Yutaka Yoshida, Yuichi Matsushima, Masahide Oku, Yuko Hirota, Tetsu Saigusa, Yoshimasa Aoki, Takeshi Uchiumi, Tadashi Yamamoto, Yasuyoshi Sakai, Dongchon Kang, Tomotake Kanki

    JOURNAL OF CELL SCIENCE   127 ( 14 )   3184 - 3196   2014.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1242/jcs.153254

  • Casein kinase 2 is essential for mitophagy Reviewed

    Tomotake Kanki, Yusuke Kurihara, Xiulian Jin, Tadahiro Goda, Yusuke Ono, Masamune Aihara, Yuko Hirota, Tetsu Saigusa, Yoshimasa Aoki, Takeshi Uchiumi, Dongchon Kang

    EMBO REPORTS   14 ( 9 )   788 - 794   2013.9

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    DOI: 10.1038/embor.2013.114

  • Mutation and functional analysis of ABCC2/multidrug resistance protein 2 in a Japanese patient with Dubin-Johnson syndrome Reviewed

    Takeshi Uchiumi, Hiroyuki Tanamachi, Kajiyo Kuchiwaki, Mitsuharu Kajita, Shinya Matsumoto, Mikako Yagi, Tomotake Kanki, Dongchon Kang

    HEPATOLOGY RESEARCH   43 ( 5 )   569 - 575   2013.5

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    DOI: 10.1111/j.1872-034X.2012.01103.x

  • Effects of overexpression of mitochondrial transcription factor A on lifespan and oxidative stress response in Drosophila melanogaster Reviewed

    Takako Matsuda, Tomotake Kanki, Teiichi Tanimura, Dongchon Kang, Etsuko T. Matsuura

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   430 ( 2 )   717 - 721   2013.1

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    DOI: 10.1016/j.bbrc.2012.11.084

  • Protein instability and functional defects caused by mutations of dihydro-orotate dehydrogenase in Miller syndrome patients Reviewed

    JingXian Fang, Takeshi Uchiumi, Mikako Yagi, Shinya Matsumoto, Rie Amamoto, Toshiro Saito, Shinya Takazaki, Tomotake Kanki, Haruyoshi Yamaza, Kazuaki Nonaka, Dongchon Kang

    BIOSCIENCE REPORTS   32 ( 6 )   631 - 639   2012.12

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    DOI: 10.1042/BSR20120046

  • p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability Reviewed

    Mikako Yagi, Takeshi Uchiumi, Shinya Takazaki, Bungo Okuno, Masatoshi Nomura, Shin-ichi Yoshida, Tomotake Kanki, Dongchon Kang

    NUCLEIC ACIDS RESEARCH   40 ( 19 )   9717 - 9737   2012.10

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    DOI: 10.1093/nar/gks774

  • Localization of mRNAs encoding human mitochondrial oxidative phosphorylation proteins Reviewed

    Shinya Matsumoto, Takeshi Uchiumi, Toshiro Saito, Mikako Yagi, Shinya Takazaki, Tomotake Kanki, Dongchon Kang

    MITOCHONDRION   12 ( 3 )   391 - 398   2012.5

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    DOI: 10.1016/j.mito.2012.02.004

  • Ribonucleoprotein Y-box-binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA Reviewed

    Shinya Matsumoto, Takeshi Uchiumi, Hiroyuki Tanamachi, Toshiro Saito, Mikako Yagi, Shinya Takazaki, Tomotake Kanki, Dongchon Kang

    BIOCHEMICAL JOURNAL   443 ( 2 )   573 - 584   2012.4

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    DOI: 10.1042/BJ20111728

  • Mitophagy Plays an Essential Role in Reducing Mitochondrial Production of Reactive Oxygen Species and Mutation of Mitochondrial DNA by Maintaining Mitochondrial Quantity and Quality in Yeast Reviewed

    Yusuke Kurihara, Tomotake Kanki, Yoshimasa Aoki, Yuko Hirota, Tetsu Saigusa, Takeshi Uchiumi, Dongchon Kang

    JOURNAL OF BIOLOGICAL CHEMISTRY   287 ( 5 )   3265 - 3272   2012.1

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    DOI: 10.1074/jbc.M111.280156

  • Phosphorylation of Serine 114 on Atg32 mediates mitophagy Reviewed

    Yoshimasa Aoki, Tomotake Kanki, Yuko Hirota, Yusuke Kurihara, Tetsu Saigusa, Takeshi Uchiumi, Dongchon Kang

    MOLECULAR BIOLOGY OF THE CELL   22 ( 17 )   3206 - 3217   2011.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1091/mbc.E11-02-0145

  • Mitochondria Autophagy in Yeast Reviewed

    Tomotake Kanki, Daniel J. Klionsky, Koji Okamoto

    ANTIOXIDANTS & REDOX SIGNALING   14 ( 10 )   1989 - 2001   2011.5

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    Language:English  

    DOI: 10.1089/ars.2010.3762

  • Nix, a receptor protein for mitophagy in mammals Reviewed

    Tomotake Kanki

    AUTOPHAGY   6 ( 3 )   433 - 435   2010.4

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    DOI: 10.4161/auto.6.3.11420

  • A genomic screen for yeast mutants defective in mitophagy Reviewed

    Tomotake Kanki, Ke Wang, Daniel J. Klionsky

    AUTOPHAGY   6 ( 2 )   278 - 280   2010.2

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    DOI: 10.1091/mbc.E09-03-0225

  • The molecular mechanism of mitochondria autophagy in yeast Reviewed

    Tomotake Kanki, Daniel J. Klionsky

    MOLECULAR MICROBIOLOGY   75 ( 4 )   795 - 800   2010.2

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    DOI: 10.1111/j.1365-2958.2009.07035.x

  • A Genomic Screen for Yeast Mutants Defective in Selective Mitochondria Autophagy Reviewed

    Tomotake Kanki, Ke Wang, Misuzu Baba, Clinton R. Bartholomew, Melinda A. Lynch-Day, Zhou Du, Jiefei Geng, Kai Mao, Zhifen Yang, Wei-Lien Yen, Daniel J. Klionsky

    MOLECULAR BIOLOGY OF THE CELL   20 ( 22 )   4730 - 4738   2009.11

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    DOI: 10.1091/mbc.E09-03-0225

  • Monitoring mitophagy in yeast The Om45-GFP processing assay Reviewed

    Tomotake Kanki, Dongchon Kang, Daniel J. Klionsky

    AUTOPHAGY   5 ( 8 )   1186 - 1189   2009.11

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    DOI: 10.4161/auto.5.8.9854

  • Atg32 is a tag for mitochondria degradation in yeast Reviewed

    Tomotake Kanki, Daniel J. Klionsky

    AUTOPHAGY   5 ( 8 )   1201 - 1202   2009.11

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    DOI: 10.4161/auto.5.8.9747

  • [Molecular mechanism of mitochondria autophagy]. Reviewed

    Kanki T

    Fukuoka igaku zasshi = Hukuoka acta medica   100 ( 9 )   291 - 297   2009.9

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    [Molecular mechanism of mitochondria autophagy].

  • Mitochondrial abnormalities drive cell death in Wolfram syndrome 2 Reviewed

    Tomotake Kanki, Daniel J. Klionsky

    CELL RESEARCH   19 ( 8 )   922 - 923   2009.8

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    DOI: 10.1038/cr.2009.94

  • Atg32 Is a Mitochondrial Protein that Confers Selectivity during Mitophagy Reviewed

    Tomotake Kanki, Ke Wang, Yang Cao, Misuzu Baba, Daniel J. Klionsky

    DEVELOPMENTAL CELL   17 ( 1 )   98 - 109   2009.7

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    DOI: 10.1016/j.devcel.2009.06.014

  • Mitophagy in Yeast Occurs through a Selective Mechanism Reviewed

    Tomotake Kanki, Daniel J. Klionsky

    JOURNAL OF BIOLOGICAL CHEMISTRY   283 ( 47 )   32386 - 32393   2008.11

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    DOI: 10.1074/jbc.M802403200

  • Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor A in mice Reviewed

    Yoshinori Hayashi, Masayoshi Yoshida, Mayumi Yamato, Tomomi Ide, Zhou Wu, Mayumi Ochi-Shindou, Tomotake Kanki, Dongchon Kang, Kenji Sunagawa, Hiroyuki Tsutsui, Hiroshi Nakanishi

    JOURNAL OF NEUROSCIENCE   28 ( 34 )   8624 - 8634   2008.8

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    DOI: 10.1523/JNEUROSCI.1957-08.2008

  • The C-terminal tail of mitochondrial transcription factor A markedly strengthens its general binding to DNA Reviewed

    Kippei Ohgaki, Tomotake Kanki, Atsushi Fukuoh, Hironori Kurisaki, Yoshimasa Aoki, Masaki Ikeuchi, Sang Ho Kim, Naotaka Hamasaki, Dongchon Kang

    JOURNAL OF BIOCHEMISTRY   141 ( 2 )   201 - 211   2007.2

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    DOI: 10.1093/jb/mvm020

  • Leigh syndrome with nephropathy and CoQ(10) deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations Reviewed

    Luis Carlos Lopez, Markus Schuelke, Catarina M. Quinzii, Tomotake Kanki, Richard J. T. Rodenburg, Ali Naini, Salvatore DiMauro, Michio Hirano

    AMERICAN JOURNAL OF HUMAN GENETICS   79 ( 6 )   1125 - 1129   2006.12

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    DOI: 10.1086/510023

  • PDIP38 associates with proteins constituting the mitochondrial DNA nucleoid Reviewed

    XL Cheng, T Kanki, A Fukuoh, K Ohgaki, R Takeya, Y Aoki, N Hamasaki, DC Kang

    JOURNAL OF BIOCHEMISTRY   138 ( 6 )   673 - 678   2005.12

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    DOI: 10.1093/jb/mvi169

  • Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA Reviewed

    T Kanki, K Ohgaki, M Gaspari, CM Gustafsson, A Fukuoh, N Sasaki, N Hamasaki, DC Kang

    MOLECULAR AND CELLULAR BIOLOGY   24 ( 22 )   9823 - 9834   2004.11

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    DOI: 10.1128/MCB.24.22.9823-9834.2004

  • Human mitochondrial DNA is packaged with TFAM Reviewed

    TI Alam, T Kanki, T Muta, K Ukaji, Y Abe, H Nakayama, K Takio, N Hamasaki, DC Kang

    NUCLEIC ACIDS RESEARCH   31 ( 6 )   1640 - 1645   2003.3

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    DOI: 10.1093/nar/gkg251

  • The N-terminal region of the transmembrane domain of human erythrocyte band 3 - Residues critical for membrane insertion and transport activity Reviewed

    T Kanki, MT Young, M Sakaguchi, N Hamasaki, MJA Tanner

    JOURNAL OF BIOLOGICAL CHEMISTRY   278 ( 8 )   5564 - 5573   2003.2

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    DOI: 10.1074/jbc.M211662200

  • The tenth membrane region of band 3 is initially exposed to the luminal side of the endoplasmic reticulum and then integrated into a partially folded band 3 intermediate Reviewed

    T Kanki, M Sakaguchi, A Kitamura, T Sato, K Mihara, N Hamasaki

    BIOCHEMISTRY   41 ( 47 )   13973 - 13981   2002.11

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    DOI: 10.1021/bi026619q

  • Diffusion-weighted images and vasogenic edema in eclampsia Reviewed

    Tomotake Kanki, Kiyomi Tsukimori, Futoshi Mihara, Hitoo Nakano

    Obstetrics and Gynecology   93 ( 5 )   821 - 823   1999.5

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    DOI: 10.1016/S0029-7844(98)00575-4

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Presentations

MISC

  • 【皮膚における細胞死:病態への関与】オートファジーの分子機構

    山下 俊一, 神吉 智丈

    皮膚科   5 ( 5 )   472 - 478   2024.5   ISSN:2436-570X

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    Authorship:Last author   Language:Japanese   Publisher:(有)科学評論社  

  • 【ミトコンドリア 疾患治療の新時代 オルガネラ動態を紐解き異常ミトコンドリアの標的分子を狙う!】(第1章)基礎研究の進展 マイトファジーの分子機構

    神吉 智丈

    実験医学   41 ( 5 )   676 - 681   2023.3   ISSN:0288-5514

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    Authorship:Lead author, Last author, Corresponding author   Language:Japanese   Publisher:(株)羊土社  

    ミトコンドリアオートファジー(マイトファジー)は,不要なミトコンドリアを選択的に分解することで,ミトコンドリアの恒常性を維持する機構である.分子機構の違いから,さらに,レセプター依存的マイトファジーとユビキチン依存的マイトファジーに分けられる.レセプター依存的マイトファジーは,恒常的なミトコンドリアのターンオーバーやミトコンドリア量の制御にかかわっており,ユビキチン依存的マイトファジーは,損傷ミトコンドリアの分解除去に働いていると考えられる.本稿では,それぞれのマイトファジーの分子機構を概説する.(著者抄録)

  • 体内の微小世界を観る~蛍光イメージングにより明かされる組織・細胞の機能構造~ ミトコンドリアオートファジーのイメージング

    神吉 智丈

    新潟医学会雑誌   136 ( 10 )   312 - 317   2022.10   ISSN:0029-0440

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    Authorship:Lead author, Last author, Corresponding author   Language:Japanese   Publisher:新潟医学会  

    ミトコンドリアは,細胞が消費するエネルギーの大半を産生する重要なオルガネラであり,その機能を維持することは細胞活動に極めて重要である.ミトコンドリアオートファジー(マイトファジー)は,オートファジーが選択的にミトコンドリアを分解することにより,ミトコンドリアの量や品質を管理していると考えられている.マイトファジーを研究し,正しく理解するためには,マイトファジーを検出できる実験系が必須である.本稿では,出芽酵母,哺乳類培養細胞,マウスにおいて,蛍光イメージングによってマイトファジーを検出する実験系を解説したい.(著者抄録)

  • 【ミトコンドリア病-病態解明を基盤とした治療薬開発】マイトファジーとミトコンドリア病

    井上 敬一, 神吉 智丈

    医学のあゆみ   281 ( 12 )   1145 - 1150   2022.6   ISSN:0039-2359

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    Authorship:Last author, Corresponding author   Language:Japanese   Publisher:医歯薬出版(株)  

    マイトファジーは、オートファジー・リソソームシステムを利用してミトコンドリアを選択的に分解することで、ミトコンドリアの品質の維持と量の調節を担うと考えられている。ミトコンドリアの機能不全が原因で起こるミトコンドリア病では、その発症過程においてマイトファジーの関与が想定される。本稿では、マイトファジーの生理機能とその分子メカニズムについて、筆者らの成果も踏まえて概説した後、後半ではマイトファジーとミトコンドリア病の関わりについて、これまでに報告された論文を中心に論じる。(著者抄録)

  • リン酸化が制御する出芽酵母のマイトファジー

    古川 健太郎, 神吉 智丈

    生化学   2019.4

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  • 【オートファジーと疾患】 ミトコンドリア恒常性の維持とマイトファジー

    山下 俊一, 神吉 智丈

    2018.7

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    マイトファジーは、異常なミトコンドリアを分解することでミトコンドリア恒常性の維持に寄与している。マイトファジーには、ParkinとPINK1が関与する経路と、マイトファジーレセプターが関与する経路に大別される。Parkin-PINK1依存的マイトファジーの発見は、パーキンソン病の原因が異常ミトコンドリアの蓄積であることを示唆している。一方、マイトファジーレセプターNIXを介したマイトファジーは赤血球の正常な分化に必要であり、NIX欠損マウスでは貧血性疾患が見られる。このように、マイトファジーの破綻が様々な疾患の原因となることが知られている。(著者抄録)

  • 【オートファジーと疾患】 Parkinに依存しないマイトファジー

    神吉 智丈

    最新医学   2017.2

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    マイトファジーは,オートファジーによる選択的ミトコンドリア分解機構である.パーキンソン病の原因遺伝子産物であるParkinとPINK1は重要なマイトファジー因子であり,精力的に研究されてきた.一方で,ParkinやPINK1がすべてのマイトファジーに必要ではなく,これらに依存しないマイトファジーの理解も重要である.ここでは,Parkinに依存しないマイトファジーに関して概説する.(著者抄録)

  • Digestシリーズ オートファジー その発見から未解決問題まで(Vol.4) 選択的オートファジー

    神吉 智丈

    2016.9

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  • 酵母におけるマイトファジーの分子機構と生理的役割

    古川 健太郎, 神吉 智丈

    化学と生物   2016.3

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  • Mitophagy in yeast: Molecular mechanisms and physiological role

    Tomotake Kanki, Kentaro Furukawa, Shun-ichi Yamashita

    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH   2015.10

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    DOI: 10.1016/j.bbamcr.2015.01.005

  • ミトコンドリアオートファジー ミトコンドリア恒常性維持機構

    神吉 智丈

    新潟医学会雑誌   2013.12

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    ミトコンドリアは、細胞活動に必須なATPの大部分を作り出す重要なオルガネラである。その機能が維持されること、即ち、ミトコンドリア恒常性維持は、細胞が正常に機能するため必須である。私たちは、新しいミトコンドリア恒常性維持機構としてミトコンドリアオートファジー(マイトファジー)に着目し研究を行ってきた。ここでは、これまでに明らかにされてきた、マイトファジーの生理的意義、疾患との関わり、分子機構を概説し、私たちが目指している、マイトファジーを用いた疾患治療への応用の可能性について簡単に紹介したい。(著者抄録)

  • マイトファジー ミトコンドリアを選択的に分解する機構

    神吉 智丈

    新潟県医師会報   2013.1

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  • 培養細胞を用いたオートファジーの活性測定法の開発とその臨床応用

    神吉 智丈, 康 東天

    臨床病理   2011.10

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  • 生化学・分子生物学 マイトファジー 基礎から臨床応用まで

    神吉 智丈, 康 東天

    医学のあゆみ   2011.7

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  • オートファジーによるミトコンドリア分解機構

    廣田 有子, 青木 義政, 神吉 智丈

    生化学   2011.2

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    出芽酵母の研究から、ミトコンドリアのオートファジーによる選択的な分解機構が明らかになりつつある。一方、哺乳類細胞の研究から、マイトファジー(オートファジーによるミトコンドリア分解)が機能低下したミトコンドリアを除去するというミトコンドリア品質管理に貢献していることが明らかになってきている。著者等は出芽酵母から、マイトファジー関連遺伝子としてATG32、ATG33を同定した。

  • ミトコンドリアオートファジーの分子機構

    神吉 智丈

    福岡医学雑誌   2009.9

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    オートファジーは飢餓を含む様々な細胞ストレスにより誘導される。ミトコンドリアのオートファジー(マイトファジー)は選択的オートファジーの一種で、傷害をうけたミトコンドリアを除去し、ミトコンドリア傷害の蓄積に起因する老化や神経変性疾患から個体を防御する機能があると考えられている。オートファジーの概論と、酵母を用いて行ったマイトファジーの解析、現在までに明らかにされてきたマイトファジーのメカニズムについて概説した。

  • Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations

    Luis Carlos Lopez, Markus Schuelke, Catarina Quinzii Hirano, Tomotake Kanki, Richard R. J. Rodenburg, Ali Naini, Salvatore Di Mauro, Michio Hirano

    NEUROLOGY   2007.3

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  • 偽膜性腸炎を契機に中毒性巨大結腸症,腸穿孔をきたした1例

    秦 奈峰子, 丸山 智義, 坂井 邦裕, 神吉 智丈, 秦 健一郎, 尼田 覚, 平川 俊夫, 加来 恒壽, 中野 仁雄

    日本産科婦人科学会雑誌   2000.10

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    子宮頸癌放射線治療後の直腸腟瘻に対する人工肛門造設術後に偽膜性腸炎を発症し中毒性巨大結腸症,腸穿孔を続発した60歳症例を経験した.本症例では偽膜性腸炎の発症後早期に診断し,薬物療法を行い,CRP値が低下し,便細菌培養およびCDトキシンが陰性化したにも拘わらず中毒性巨大結腸症,さらには腸穿孔をきたし外科的治療を必要とした.これは,炎症が高度で,全層に及び漿膜まで波及していたために,炎症が鎮静化した時点で既に筋は弛緩し腸管は拡張していたものと考えられる.また偽膜性腸炎の発症と炎症の重症化に,汎血球減少という宿主側の生体防御能の低下も大きく関与していた可能性が考えられた

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Professional Memberships

  • THE JAPANESE SOCIETY OF MITOCHONDRIAL RESEARCH AND MEDICINE

  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

  • THE JAPANESE BIOCHEMICAL SOCIETY

  • JAPAN SOCIETY OF OBSTETRICS AND GYNECOLOGY

  • JAPAN SOCIETY FOR CELL BIOLOGY

  • 酵母遺伝学フォーラム

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Research Projects

  • Genomic regulation of intracellular symbiotic organelles: from technological innovation to understanding and application of life phenomena

    Grant number:24H02270  2024.4 - 2029.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Transformative Research Areas (A)

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    Authorship:Coinvestigator(s)  Grant type:Scientific research funding

    CiNii Research

  • ミトコンドリアゲノムの母性遺伝・動態・品質管理機構の解明

    Grant number:24H02274  2024.4 - 2029.3

    科学研究費助成事業  学術変革領域研究(A)

    佐藤 美由紀, 神吉 智丈

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    Authorship:Principal investigator  Grant type:Scientific research funding

    ミトコンドリアゲノム(mtDNA)に特有の「母性遺伝」や「ヘテロプラスミー」といった遺伝様式の理解は,生物学的にも,また治療法が確立していないミトコンドリア病を理解するためにも必須である.本研究ではマウス,線虫,酵母といった多彩な生物種においてmtDNA編集系を構築し,mtDNAの遺伝的特殊性を解析するためのモデル生物を作製する.また, mtDNA制御機構にミトコンドリア品質管理機構であるマイトファジーという新たな視点を導入し,母性遺伝における父性ミトコンドリア選択的分解機構の分子基盤や生理的意義の解明,ヘテロプラスミーを維持する機構の解明とミトコンドリア病モデル生物への応用を目指す.

    CiNii Research

  • Elucidation of the mechanism of mitochondrial fission driven by novel factors

    Grant number:24K01717  2024.4 - 2027.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant type:Scientific research funding

    CiNii Research

  • レセプター依存的マイトファジーの誘導制御と生理機能の解明 研究課題

    2022.4 - 2025.3

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    Authorship:Principal investigator 

  • レセプター依存的マイトファジーの誘導制御と生理機能の解明

    Grant number:23K23878  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    神吉 智丈, 井上 敬一, 山下 俊一, 福田 智行

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    Authorship:Principal investigator  Grant type:Scientific research funding

    ミトコンドリアは、細胞が必要とするエネルギーを作る非常に重要な場所である。従来の研究は、ミトコンドリアがどのようにして作られてくるかに着目していたが、本研究は、機能が悪くなったミトコンドリアを取り除く(分解する)現象であるマイトファジーに着目し、その生理機能を明らかにしようとするものである。具体的には、マイトファジーの誘導が抑制された培養細胞やマウスを用いて、どのような異常が生じるのかを観察する。

    CiNii Research

Class subject

  • 生理学

    2024.4 - 2025.3   Full year

FD Participation

  • 2024.4   Role:Participation   Title:令和6年度第1回全学FD(新任教員研修)

    Organizer:University-wide

Visiting, concurrent, or part-time lecturers at other universities, institutions, etc.

  • 2024  新潟大学大学院医歯学総合研究科  Classification:Affiliate faculty  Domestic/International Classification:Japan