Regulation of the heat shock response by mitochondrial signals

• Project/Area Number: 15H04706
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Yamaguchi University
• Principal Investigator: NAKAI Akira 山口大学, 大学院医学系研究科, 教授 (60252516)
• Co-Investigator(Kenkyū-buntansha): 藤本 充章 山口大学, 大学院医学系研究科, 准教授 (80359900) ; 瀧井 良祐 山口大学, 大学院医学系研究科, 助教 (00419558)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: protein homeostasis / heat shock / chaperone / transcription / mitochondria / HSF1 / SSBP1 / シャペロン / 転写 / ストレス / ミトコンドリア / プロテオスタシス / 熱ストレス

Outline of Final Research Achievements

In response to proteotoxic stresses including heat shock, cells maintain protein homeostasis through an adaptive response called the heat shock response. This response is regulated at a level of transcription by heat shock transcription factor 1 (HSF1). We here show that HSF1 interacts with SSBP1, which is involved in replication and metabolism of mitochondrial DNA. Furthermore, HSF1-SSBP1 accumulates in the nucleus and maintains mitochondrial function during proteotoxic stress.

Research Products

• [Int'l Joint Research] Children's National Medical Center/Yale University School of Medicine/George Washington University(米国)
• [Journal Article] Inhibition of gingipains prevents Porphyromonas gingivalis-induced preterm birth and fetal death in pregnant mice. (2018)
  • Author(s): Takii R, Kadowaki T, Tsukuba T, Yamamoto K.
  • Journal Title: European Journal of Pharmacology Volume: 824 Pages: 48-56
  • DOI: 10.1016/j.ejphar.2018.01.028
  • Peer Reviewed / Open Access
• [Journal Article] Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling (2017)
  • Author(s): Ishii Seiji、Torii Masaaki、Son Alexander I.、Rajendraprasad Meenu、Morozov Yury M.、Kawasawa Yuka Imamura、Salzberg Anna C.、Fujimoto Mitsuaki、Brennand Kristen、Nakai Akira、Mezger Valerie、Gage Fred H.、Rakic Pasko、Hashimoto-Torii Kazue
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 15157-15157
  • DOI: 10.1038/ncomms15157
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Heat Shock Factor 1 in Conserving Cholesterol Transportation in Leydig Cell Steroidogenesis via Steroidogenic Acute Regulatory Protein. (2017)
  • Author(s): Oka S, Shiraishi K, Fujimoto M, Katiyar A, Takii R, Nakai A, Matsuyama H.
  • Journal Title: Endocrinology Volume: 158 Issue: 8 Pages: 2648-2658
  • DOI: 10.1210/en.2017-00132
  • Peer Reviewed / Open Access
• [Journal Article] HSF1 and HSF3 cooperatively regulate the heat shock response in lizards (2017)
  • Author(s): Takii Ryosuke、Fujimoto Mitsuaki、Matsuura Yuki、Wu Fangxu、Oshibe Namiko、Takaki Eiichi、Katiyar Arpit、Akashi Hiroshi、Makino Takashi、Kawata Masakado、Nakai Akira
  • Journal Title: PLOS ONE Volume: 12 Issue: 7 Pages: e0180776-e0180776
  • DOI: 10.1371/journal.pone.0180776
  • Peer Reviewed / Open Access
• [Journal Article] The HSF1-PARP13-PARP1 complex facilitates DNA repair and promotes mammary tumorigenesis (2017)
  • Author(s): Fujimoto Mitsuaki、Takii Ryosuke、Takaki Eiichi、Katiyar Arpit、Nakato Ryuichiro、Shirahige Katsuhiko、Nakai Akira
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1638-1638
  • DOI: 10.1038/s41467-017-01807-7
  • Peer Reviewed / Open Access
• [Journal Article] Long-term melatonin treatment delays ovarian aging. (2017)
  • Author(s): Tamura H, Kawamoto M, Sato S, Tamura I, Maekawa R, Taketani T, Aasada H, Takaki E, Nakai A, Reiter RJ, Sugino N.
  • Journal Title: Journal of Pineal Research Volume: 印刷中 Issue: 2
  • DOI: 10.1111/jpi.12381
  • Peer Reviewed / Open Access
• [Journal Article] Anti-TNF-α agent infliximab and splenectomy are protective against renal ischemia-reperfusion injury. (2016)
  • Author(s): Y. Nagata, M. Fujimoto, K. Nakamura, N. Isoyama, M. Matsumura, K. Fujikawa, K. Uchiyama, E. Takaki, R. Takii, A. Nakai, and H. Matsuyama.
  • Journal Title: Transplantation Volume: 100 Issue: 8 Pages: 1675-1682
  • DOI: 10.1097/tp.0000000000001222
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Heat shock transcription factor 1-associated expression of slow myosin heavy chain in mouse soleus muscle in response to unloading with or without reloading (2016)
  • Author(s): Yokoyama S, Ohno Y, Egawa T, Yasuhara K, Nakai A, Sugiura T, Ohira Y, Yoshioka T, Okita M, Origuchi T, Goto K
  • Journal Title: Acta Physiol (Oxf) Volume: 217 Issue: 4 Pages: 325-337
  • DOI: 10.1111/apha.12692
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of the novel mutant A78T-HERG from a long QT syndrome type 2 patient: Instability of the mutant protein and stabilization by heat shock factor 1. (2016)
  • Author(s): Kondo T., Hisatome I., Yoshimura S., Mahati E., Notsu T., Li P., Iitsuka K., Kato M., Ogura K., Miake J., Aiba T., Shimizu W., Kurata Y., Sakata S., Nakasone N., Ninomiya H., Nakai A., Higaki K., Kawata Y., Shirayoshi Y., Yoshida A., Yamamoto K.
  • Journal Title: Journal of Arrhythmia Volume: 32 Issue: 5 Pages: 433-440
  • DOI: 10.1016/j.joa.2015.10.005
  • NAID: 120007146982
  • Peer Reviewed / Open Access
• [Journal Article] M3 Muscarinic Receptor Signaling Stabilizes a Novel Mutant Human Ether-a-Go-Go-Related Gene Channel Protein via Phosphorylation of Heat Shock Factor 1 in Transfected Cells (2016)
  • Author(s): Mahati E., Li P., Kurata Y., Maharani N., Nobuhito I., Sakata S., Ogura K., Miake J., Aiba T., Shimizu W., Nakasone N., Ninomiya H., Higaki K., Yamamoto K., Nakai A., Shirayoshi Y., Hisatome I.
  • Journal Title: Circulation Journal Volume: 80 Issue: 12 Pages: 2443-2452
  • DOI: 10.1253/circj.CJ-16-0712
  • NAID: 130005284978
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] A study of hearing function and histopathologic changes in the cochlea of the type 2 diabetes model Tsumura Suzuki obese diabetes mouse. (2016)
  • Author(s): Tsuda J, Sugahara K, Hori T, Kanagawa E, Takaki E, Fujimoto M, Nakai A, Yamashita H.
  • Journal Title: Acta Otolaryngology Volume: 136 Issue: 11 Pages: 1097-1106
  • DOI: 10.1080/00016489.2016.1195012
  • Peer Reviewed
• [Journal Article] Molecular basis of HSF regulation. (2016)
  • Author(s): A. Nakai
  • Journal Title: Nature Structural & Molecular Biology Volume: 23 Issue: 2 Pages: 93-95
  • DOI: 10.1038/nsmb.3165
• [Journal Article] Fatty acid-binding protein 7 regulates function of caveolae in astrocytes through expression of caveolin-1. (2015)
  • Author(s): Yoshiteru Kagawa, Yuki Yasumoto, Kazem Sharifi, Majid Ebrahimi, Ariful Islam, Hirofumi Miyazaki, Yui Yamamoto, Tomoo Sawada, Hiroko Kishi, Sei Kobayashi, Motoko Maekawa, Takeo Yoshikawa, Eiichi Takaki, Akira Nakai, Hiroshi Kogo, Toyoshi Fujimoto and Yuji Owada
  • Journal Title: Glia Volume: 63 Issue: 5 Pages: 780-794
  • DOI: 10.1002/glia.22784
  • Peer Reviewed / Open Access
• [Journal Article] Heat shock protein 90 associates with Toll-like receptors 7/9 and mediates self-nucleic acid recognition in SLE. (2015)
  • Author(s): Saito K, Kukita K, Kutomi G, Okuya K, Asanuma H, Tabeya T, Naishiro Y, Yamamoto M, Takahashi H, Torigoe T, Nakai A, Shinomura Y, Hirata K, Sato N, Tamura Y.
  • Journal Title: Eur. J Immunology Volume: 0 Issue: 7 Pages: 0-0
  • DOI: 10.1002/eji.201445293
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Retinoic acid has the potential to suppress endometriosis development. (2015)
  • Author(s): Yamagata Y, Takaki E, Shinagawa M, Okada M, Jozaki K, Lee L, Sato S, Maekawa R, Taketani T, Asada H, Tamura H, Nakai A, Sugino N.
  • Journal Title: J Ovarian Res. Volume: 8 Issue: 1 Pages: 49-49
  • DOI: 10.1186/s13048-015-0179-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice (2015)
  • Author(s): Ohno Y, Egawa T, Yokoyama S, Nakai A, Sugiura T, Ohira Y, Yoshioka T, Goto K
  • Journal Title: Acta Physiol (Oxf) Volume: 215 Issue: 4 Pages: 191-203
  • DOI: 10.1111/apha.12600
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] ミトコンドリアのプロテオスタシス制御 (2015)
  • Author(s): 譚克、中井彰
  • Journal Title: 生化学 Volume: 87 Pages: 758-761
  • NAID: 40020687468
• [Presentation] HSF1転写複合体解析による熱ショック応答機構の解明 (2017)
  • Author(s): 瀧井良祐、藤本充章、Arpit Katiyar、松本雅記、中井 彰
  • Organizer: 冬の若手ワークショップ2017
  • Place of Presentation: 一宮シーサイドオーツカ（千葉県・長生郡）
  • Year and Date: 2017-01-30
• [Presentation] HSF1 in Stress and Health (2017)
  • Author(s): Akira Nakai
  • Organizer: TARA seminar, Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba
  • Invited
• [Presentation] HSF1 mediates DNA damage response by assisting with the redistribution of PARP1 (2017)
  • Author(s): Akira Nakai
  • Organizer: 8th International Congress on Stress Responses in Biology & Medicine
  • Int'l Joint Research / Invited
• [Presentation] Regulation of heat shock response by HSF1-PARP complex in mammalian cells (2017)
  • Author(s): Mitsuaki Fujimoto, Ryosuke Takii, Arpit Katiyar, and Akira Nakai
  • Organizer: 8th International Congress on Stress Responses in Biology & Medicine
• [Presentation] HSF1 and HSF3 cooperatively regulate the heat shock response in lizards (2017)
  • Author(s): Ryosuke Takii, Mitsuaki Fujimoto, Arpit Katiyar, Pratibha Srivastava, and Akira Nakai
  • Organizer: 8th International Congress on Stress Responses in Biology & Medicine
• [Presentation] HSF1の新たな機能とがん (2017)
  • Author(s): 藤本充章、中井 彰
  • Organizer: 第34回日本ハイパーサーミア学会
  • Invited
• [Presentation] HSF1の活性調節に働くリン酸化部位Ser326は進化的に保存されている (2017)
  • Author(s): 瀧井良祐、藤本充章、Arpit Katiyar、Pratibha Srivastava、中井 彰
  • Organizer: 第12回臨床ストレス応答学会大会
• [Presentation] 染色体関連因子による熱ショック応答の制御 (2017)
  • Author(s): 瀧井良祐、中井 彰
  • Organizer: 2017年度 生命科学系学会合同年次大会 ワークショップ「プロテオスタシス制御の新展開と疾患」
  • Invited
• [Presentation] HSF1-PARP複合体による熱ショック応答の調節 (2017)
  • Author(s): 藤本充章、瀧井良祐、Katiyar Arpit、Srivastava Pratibha, 中井 彰
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] HSF1 in co-operation with SSBP1 regulates mitochondrial proteotoxic stress response in mammals (2017)
  • Author(s): Katiyar Arpit, Mitsuaki Fujimoto, Ryosuke Takii, Pratibha Srivastava, and Akira Nakai
  • Organizer: 2017年度 生命科学系学会合同年次大会
• [Presentation] 熱ショック応答と神経疾患およびがん (2017)
  • Author(s): 中井 彰
  • Organizer: 理研セミナー
  • Invited
• [Presentation] 熱ショック応答とDNA修復機構 (2017)
  • Author(s): 藤本充章
  • Organizer: 群馬大学生体調節研究所 内分泌・代謝学共同利用共同研究拠点セミナー
  • Invited
• [Presentation] HSF1転写複合体の同定と機能解析 (2016)
  • Author(s): 瀧井良祐、藤本充章、Arpit Katiyar、松本雅記、中井 彰
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-11-30
• [Presentation] HSF1 is a common regulator of cytoplasmic and mitochondria-specific proteotoxic stress responses in mammals. (2016)
  • Author(s): Arpit Katiyar, Mitsuaki Fujimoto, Ryosuke Takii, and Akira Nakai.
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-11-30
• [Presentation] Anti-TNFa agent Infliximab and splenectomy are protective against renal ischemia-reperfusion injury. (2016)
  • Author(s): 永田雄大、磯山直仁、内山浩一、中井 彰、松山豪泰
  • Organizer: 第68回西日本泌尿器科学会総会
  • Place of Presentation: 海峡メッセ下関（山口県・下関市）
  • Year and Date: 2016-11-24
• [Presentation] 熱ショック応答におけるポリADPリボシル化酵素の役割 (2016)
  • Author(s): 藤本 充章、瀧井良祐、Arpit Katiyar、中井 彰
  • Organizer: 第11回臨床ストレス応答学会大会
  • Place of Presentation: 山口大学（山口県・宇部市）
  • Year and Date: 2016-11-11
  • Invited
• [Presentation] HSF1 is a regulator of mitochondrial HSP genes in mammals. (2016)
  • Author(s): Arpit Katiyar, Mitsuaki Fujimoto, Ryosuke Takii, Ke Tan, and Akira Nakai.
  • Organizer: 第11回臨床ストレス応答学会大会
  • Place of Presentation: 山口大学（山口県・宇部市）
  • Year and Date: 2016-11-11
• [Presentation] マウスLeydig細胞でのステロイド合成におけるHSF1の役割 (2016)
  • Author(s): 岡 真太郎、白石弘司、藤本充章、Arpit Katiyar、瀧井良祐、中井 彰、松山豪泰
  • Organizer: 第11回臨床ストレス応答学会大会
  • Place of Presentation: 山口大学（山口県・宇部市）
  • Year and Date: 2016-11-11
• [Presentation] HSF1-SSBP1 complex maintains mitochondrial function via upregulation of NRF1 expression during heat shock. (2016)
  • Author(s): Ke Tan, Yumei Fan, Arpit Katiyar, Mitsuaki Fujimoto, Ryosuke Takii, Akira Nakai, and Xianglin Duan.
  • Organizer: 第11回臨床ストレス応答学会大会
  • Place of Presentation: 山口大学（山口県・宇部市）
  • Year and Date: 2016-11-11
• [Presentation] HSF1転写複合体による細胞の恒常性維持機構 (2016)
  • Author(s): 中井 彰
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市））
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] 進化的アプローチによる熱ショック因子HSF1転写複合体の同定 (2016)
  • Author(s): 瀧井良祐、藤本充章、高木栄一、Arpit Katiyar、松本雅記、中井 彰
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-09-25
• [Presentation] 熱ショック応答によるミトコンドリアのプロテオスタシス制御 (2016)
  • Author(s): 中井 彰
  • Organizer: 第12回レドックス・ライフイノベーションシンポジウム
  • Place of Presentation: 熊本大学（熊本県・熊本市）
  • Year and Date: 2016-08-18
  • Invited
• [Presentation] HSF1-PARP複合体はDNA損傷応答に関与する (2016)
  • Author(s): 藤本充章、瀧井良祐、高木栄一、Arpit Katiyar、中井 彰
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
• [Presentation] Regulation of proteostasis and the heat shock response. (2016)
  • Author(s): Akira Nakai
  • Organizer: College of Life Science, Hebei Normal University
  • Place of Presentation: Shijiazhuang, China
  • Invited
• [Presentation] タンパク質毒性ストレス応答とDNA損傷ストレス応答の接点 (2015)
  • Author(s): 藤本充章、中井彰
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会大会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] 進化的アプローチによる熱ショック因子HSF1の転写関連領域の解析 (2015)
  • Author(s): 瀧井良祐、藤本充章、高木栄一、譚克、中井 彰
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会大会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2015-12-01
• [Presentation] マウス視床下部における熱ショック因子HSF4の解析 (2015)
  • Author(s): 高木栄一、藤本充章、瀧井良祐、譚克、中井 彰
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会大会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2015-12-01
• [Presentation] Pathological brain development elicited heterogenous activation of stress responsive signaling under exposure to environmental stress. (2015)
  • Author(s): Seiji Ishii, Alexander I. Son, Meenu Rajendraprasad, Yury Morozov, Mitsuaki Fujimoto, Kristen Brennand, Akira Nakai, Valerie Mezger, Fred Gage, Masaaki Torii, Pasko Rakic, Kazue Hashimoto-Torii.
  • Organizer: 第88回日本生化学会大会・第38回日本分子生物学会大会
  • Place of Presentation: 神戸国際会議場、神戸
  • Year and Date: 2015-12-01
• [Presentation] 腎虚血再灌流障害における脾臓摘出および抗TNF-α製剤の効果 (2015)
  • Author(s): 永田雄大、中村公彦、磯山直仁、松村正文、藤川公樹、内山浩一、中井 彰、松山豪泰
  • Organizer: 臨床ストレス応答学会
  • Place of Presentation: 東京農工大学、東京
  • Year and Date: 2015-11-06
• [Presentation] Heat shock response is modulated by poly(ADP-ribose) polymerases in mammalian cells. (2015)
  • Author(s): A. Nakai
  • Organizer: The 7th international congress on stress response in biology and medicine
  • Place of Presentation: Huangshan, China
  • Year and Date: 2015-09-15
  • Int'l Joint Research / Invited
• [Presentation] Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity. (2015)
  • Author(s): Ke Tan, Mitsuaki Fujimoto, Ryosuke Takii, Eiichi Takaki, Akira Nakai
  • Organizer: The 7th international congress on stress response in biology and medicine
  • Place of Presentation: Huangshan, China
  • Year and Date: 2015-09-15
  • Int'l Joint Research
• [Book] Heat Shock Factor (2016)
  • Author(s): A. Nakai
  • Total Pages: 301
  • Publisher: Springer, Japan
• [Book] 南山堂医学大事典 (2015)
  • Author(s): 中井 彰、他
  • Total Pages: 3101
  • Publisher: 南山堂
• [Remarks] 山口大学大学院医学系研究科医化学講座
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/
• [Remarks] 山口大学大学院医学系研究科 医化学講座
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/
• [Remarks] 医化学研究室ホームページ
  • URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/