Molecular Mechanism of co-ordinately translational regulation between outer and inner mitochondria

• Project/Area Number: 21590337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: UCHIUMI Takeshi 九州大学, 医学研究院, 准教授 (80253798)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ミトコンドリア / 翻訳 / 酸化的リン酸化 / YB-1

Research Abstract

Mitochondria play key roles in essential cellular functions such as energy production, metabolic pathways and aging. Growth factor-mediated expression of the mitochondrial oxidative phosphorylation(OXPHOS) complex proteins has been proposed to play a fundamental role in metabolic homeostasis. Although protein translation is affected by general RNA-binding proteins, very little is known about the mechanism involved in mitochondrial OXPHOS protein translation. In the present study, serum stimulation induced the nuclear-encoded OXPHOS protein expression such as NDUFA9, NDUFB8, SDHB and UQCRFS1 and mitochondrial ATP production in translation-dependent manners. We also observed that the major mRNA ribonucleoprotein Y-box binding protein-1(YB-1) preferentially bound to these OXPHOS mRNA and regulated the recruitment of mRNAs from inactive messenger ribonucleoprotein particles(mRNPs) to active polysomes. YB-1 depletion led to upregulation of mitochondrial function through induction of OXPHOS protein translation from mRNP release. In contrast, YB-1 overexpression suppressed the translation of these OXPHOS mRNAs through reduced polysome formation, suggesting that YB-1 regulated the translation of mitochondrial OXPHOS mRNAs through mRNA binding. Taken together, our findings suggest that YB-1 is a critical factor for translation that may control OXPHOS activity.

Research Products

• [Journal Article] Ribonucleoprotein Y-box binding protein-1 regulates mitochondrial oxidative phosphorylationprotein expression after serum stimulation through binding to OXPHOS mRNA (2012)
  • Author(s): Matsumoto S, Uchiumi T, Tanamachi H, Saito T, Yagi M, Takazaki S, Kanki T, Kang D.
  • Journal Title: Biochem J. Volume: 12 Pages: 391-398
• [Journal Article] oxidative stress by androgen deprivation and prevents conversion from androgen dependent to castration resistant prostate cancer (2012)
  • Author(s): Shiota M, Song Y, Takeuchi A, Yokomizo A, Kashiwagi E, Kuroiwa K, Tatsugami K, Uchiumi T, Oda Y, Naito S.
  • Journal Title: J Urol. Volume: 187 Pages: 707-14
• [Journal Article] 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 (2012)
  • Author(s): Kurihara Y, Kanki T, Aoki Y, Hirota Y, Saigusa T, Uchiumi T, Kang D.
  • Journal Title: J Biol Chem Volume: 287 Pages: 3265-72
• [Journal Article] The role of TFAM-associated proteins in mitochondrial RNA metabolism (2012)
  • Author(s): Uchiumi T, Kang D.
  • Journal Title: Biochim Biophys Acta Volume: 1820 Pages: 565-70
• [Journal Article] Ribonucleoprotein Y-box binding protein-1 regulates mitochondrial oxidative phosphorylation (OXPHOS) protein expression after serum stimulation through binding to OXPHOS mRNA (2012)
  • Author(s): Matsumoto S, Uchiumi T, et al
  • Journal Title: Biochemical J Volume: 443 Issue: 2 Pages: 573-584
  • DOI: 10.1042/bj20111728
  • Peer Reviewed
• [Journal Article] Antioxidant therapy alleviates oxidative stress by androgen deprivation and prevents conversion from androgen dependent to castration resistant prostate cancer (2012)
  • Author(s): Shiota M, Song Y, Takeuchi A, Yokomizo A, Kashiwagi E, Kuroiwa K, Tatsugami K, Uchiumi T, Oda Y, Naito S
  • Journal Title: Journal Urology Volume: 187 Issue: 2 Pages: 707-714
  • DOI: 10.1016/j.juro.2011.09.147
  • Peer Reviewed
• [Journal Article] The role of TFAM-associated proteins in mitochondrial RNA metabolism (2012)
  • Author(s): Uchiumi T, Kang D
  • Journal Title: Biochim Biophys Acta Volume: 1820 Issue: 5 Pages: 565-570
  • DOI: 10.1016/j.bbagen.2011.08.014
  • Peer Reviewed
• [Journal Article] 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 (2012)
  • Author(s): Kurihara Y, Kanki T, Aoki Y, Hirota Y, Saigusa T, Uchiumi T, Kang D
  • Journal Title: J Biol Chem Volume: 287 Issue: 5 Pages: 3265-3272
  • DOI: 10.1074/jbc.m111.280156
  • Peer Reviewed
• [Journal Article] Phosphorylation of Serine 114 on Atg32 mediates mitophagy (2011)
  • Author(s): Aoki Y, Kanki T, Hirota Y, Kurihara Y, Saigusa T, Uchiumi T, Kang D.
  • Journal Title: Mol Biol Cell Volume: 22 Pages: 3206-17
• [Journal Article] YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth (2011)
  • Author(s): Fotovati A, Abu-Ali S, Wang PS, Deleyrolle LP, Lee C, Triscott J, Chen JY, Franciosi S, Nakamura Y, Sugita Y, Uchiumi T, Kuwano M, Leavitt BR, Singh SK, Jury A, Jones C, Wakimoto H, Reynolds BA, Pallen CJ, Dunn SE.
  • Journal Title: Cancer Res Volume: 71 Pages: 5569-78
• [Journal Article] Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression (2011)
  • Author(s): Shiota M, Takeuchi A, Song Y, Yokomizo A, Kashiwagi E, Uchiumi T, Kuroiwa K, Tatsugami K, Fujimoto N, Oda Y, Naito S.
  • Journal Title: Endocr Relat Cancer Volume: 18 Pages: 505-17
• [Journal Article] Peroxiredoxin 2 in the nucleus and cytoplasm distinctly regulates androgen receptor activity in prostate cancer cells (2011)
  • Author(s): Shiota M, Yokomizo A, Kashiwagi E, Takeuchi A, Fujimoto N, Uchiumi T, Naito S.
  • Journal Title: Free Radic Biol Med Volume: 51 Pages: 78-87
• [Journal Article] Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter PSA relapse time after radical prostatectomy. (2011)
  • Author(s): Amamoto R, Yagi M, Song Y, Oda Y, Tsuneyoshi M, Naito S, Yokomizo A, Kuroiwa K, Tokunaga S, Kato S, Hiura H, Samori T, Kang D, Uchiumi T.
  • Journal Title: Cancer Sci Volume: 102 Pages: 639-647
• [Journal Article] YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth (2011)
  • Author(s): Fotovati A, Abu-Ali S Sugita Y, Uchiumi T, et al
  • Journal Title: Cancer Res Volume: 71 Issue: 16 Pages: 5567-5578
  • DOI: 10.1158/0008-5472.can-10-2805
  • Peer Reviewed
• [Journal Article] Mitochondrial p32/C1QBP is highly expressed in prostate cancer and is associated with shorter PSA relapse time after radical prostatectomy (2011)
  • Author(s): Amamoto R, Yagi M, Song Y, Oda Y, Tsuneyoshi M, Naito S, Yokomizo A, Kuroiwa K, Tokunaga S, Kato S, Hiura H, Samori T, Kang D, Uchiumi T
  • Journal Title: Cancer Sci Volume: 102 Issue: 3 Pages: 639-647
  • DOI: 10.1111/j.1349-7006.2010.01828.x
  • Peer Reviewed
• [Journal Article] Castration resistance of prostate cancer cells caused by castration-induced oxidative stress through Twist1 and androgen receptor overexpression (2010)
  • Author(s): Shiota M, Yokomizo A, Tada Y, Inokuchi J, Kashiwagi E, Masubuchi D, Eto M, Uchiumi T, Naito S.
  • Journal Title: Oncogene Volume: 29 Pages: 237-250
• [Journal Article] Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus (2010)
  • Author(s): Shiota M, Yokomizo A, Masubuchi D, Tada Y, Inokuchi J, Eto M, Uchiumi T, Fujimoto N, Naito S.
  • Journal Title: Prostate Volume: 70 Pages: 540-554
• [Journal Article] Peroxisome proliferator-activated receptor gamma coactivator-1alpha interacts with the androgen receptor(AR) and promotes prostate cancer cell growth by activating the AR (2010)
  • Author(s): Shiota M, Yokomizo A, Tada Y, Inokuchi J, Tatsugami K, Kuroiwa K, Uchiumi T, Fujimoto N, Seki N, Naito S.
  • Journal Title: Mol Endocrinol Volume: 24 Pages: 114-127
• [Journal Article] ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation (2010)
  • Author(s): Uchiumi T, Ohgaki K, Yagi M, Aoki Y, Sakai A, Matsumoto S, Kang D.
  • Journal Title: Nucleic Acids Res Volume: 38 Pages: 5554-5568
  • NAID: 120005227389
• [Journal Article] P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance. (2010)
  • Author(s): Shiota M, Yokomizo A, Tada Y, Uchiumi T, Inokuchi J, Tatsugami K, Kuroiwa K, Yamamoto K, Seki N, Naito S.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1797-1806
  • NAID: 10027830401
• [Journal Article] Sorafenib with doxorubicin augments cytotoxicity to renal cell cancer through PERK inhibition (2010)
  • Author(s): Shiota M, Eto M, Yokomizo A, Tada Y, Takeuchi A, Masubuchi D, Inokuchi J, Tatsugami K, Kuroiwa K, Uchiumi T, Seki N, Naito S.
  • Journal Title: Int J Oncol. Volume: 36 Pages: 1521-1531
• [Journal Article] Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell-cycle-associated genes (2010)
  • Author(s): Izumi H, Wakasugi T, Shimajiri S, Tanimoto A, Sasaguri Y, Kashiwagi E, Yasuniwa Y, Akiyama M, Han B, Wu Y, Uchiumi T, Arao T, Nishio K, Yamazaki R, Kohno K.
  • Journal Title: Cancer Sci Volume: 101 Pages: 2538-2545
  • NAID: 10027834347
• [Journal Article] Sensitivity of doxorubicin-resistant cells to sorafenib : possible role for inhibition of eukaryotic initiation factor-2alpha phosphorylation. (2010)
  • Author(s): Shiota M, Eto M, Yokomizo A, Tada Y, Takeuchi A, Itsumi M, Tatsugami K, Uchiumi T, Naito S.
  • Journal Title: Int J Oncol Volume: 37 Pages: 509-517
• [Journal Article] Human heterochromatin protein 1 isoform HP1beta enhances androgen receptor activity and is implicated in prostate cancer growth (2010)
  • Author(s): Shiota M, Song Y, Yokomizo A, Tada Y, Kuroiwa K, Eto M, Oda Y, Inokuchi J, Uchiumi T, Fujimoto N, Seki N, Naito S.
  • Journal Title: Endocr Relat Cancer Volume: 17 Pages: 455-67
• [Journal Article] Foxo3a expression and acetylation regulate cancer cell growth and sensitivity to cisplatin (2010)
  • Author(s): Shiota M, Yokomizo A, Kashiwagi E, Tada Y, Inokuchi J, Tatsugami K, Kuroiwa K, Uchiumi T, Seki N, Naito S.
  • Journal Title: Cancer Sci Volume: 101 Pages: 1177-1185
  • NAID: 10026592158
• [Journal Article] Foxo3a suppression of urothelial cancer invasiveness through Twist1, Y-box-binding protein 1, and E-cadherin regulation. Clin (2010)
  • Author(s): Shiota M, Song Y, Yokomizo A, Kiyoshima K, Tada Y, Uchino H, Uchiumi T, Inokuchi J, Oda Y, Kuroiwa K, Tatsugami K, Naito S.
  • Journal Title: Cancer Res Volume: 16 Pages: 5654-5663
• [Journal Article] ERAL1 is associated with mitochondrial ribosome and elimination of ERAL1 leads to mitochondrial dysfunction and growth retardation. (2010)
  • Author(s): Uchiumi T, Ohgaki K, Yagi M, Aoki Y, Sakai A, Matsumoto S, Kang D
  • Journal Title: Nucleic Acids Res Volume: 38 Pages: 5554-5568
  • NAID: 120005227389
  • Peer Reviewed
• [Journal Article] Peroxisome proliferator-activated receptor gamma coactivatorlalpha interacts with the androgen receptor (AR) and promotes prostate cancer cell growth by activating the AR (2010)
  • Author(s): Shiota M, Uchiumi T, et al
  • Journal Title: Mol Endocrinol 24 Pages: 114-127
  • Peer Reviewed
• [Journal Article] DNA conformation-dependent activities of human mitochondrial RNA polymerase. (2009)
  • Author(s): Fukuoh A, Ohgaki K, Hatae H, Kuraoka I, Aoki Y, Uchiumi T, Jacobs HT, Kang D.
  • Journal Title: Genes Cells Volume: 14 Pages: 1029-1042
• [Journal Article] DNA conformation-dependent activities of human mitochondrial RNA polymerase (2009)
  • Author(s): Fukuoh A, Uchiumi T, et al
  • Journal Title: Gene to cell 14 Pages: 1029-42
  • Peer Reviewed
• [Presentation] 前立腺がんで発現亢進するミトコンドリアRNA結合蛋白p32の機能解析 (2011)
  • Author(s): 内海健、康東天
  • Organizer: 第58回日本臨床検査医学会
  • Place of Presentation: 岡山
  • Year and Date: 2011-09-21
• [Presentation] Embryonic lethality in mitochondrial p32 deficient, and the importance of p32 RNA binding for OXPHOS (2011)
  • Author(s): Takeshi Uchiumi, Mikako Yagi, Dongchon Kang
  • Organizer: 第34回日本分子生物学会パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] Ribonucleoprotein YB-1 binds to mitochondrial oxidative phosphorylation(OXPHOS) mRNA and regulate OXPHOS protein expression after serum stimulation (2011)
  • Author(s): Shinya Matsumoto, Takeshi Uchiumi, Dongchon Kang
  • Organizer: 第34回日本分子生物学会パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] ミトコンドリアRNA結合蛋白p32の機能解析 (2011)
  • Author(s): 内海健
  • Organizer: 第84回日本生化学会、京都国際会館
  • Place of Presentation: 京都
• [Presentation] 前立腺がんで発現亢進するミトコンドリアRNA結合蛋白p32の機能解析 (2011)
  • Author(s): 内海健、康東天
  • Organizer: 第58回日本臨床検査医学会岡山コンベンションセンター
  • Place of Presentation: 岡山
• [Presentation] Mitochondrial p32 is highly expressed in prostate cancer and is associated with shorter PSA relapse (2011)
  • Author(s): Takeshi Uchiumi, Rie Amamoto, Dongchon Kang
  • Organizer: EuroMit 8 European Meeting on Mitochondrial Pathology, Zaragoza
  • Place of Presentation: Spain
• [Presentation] ミトコンドリア蛋白p32/C1qBPは前立腺がんで高発現し予後マーカーとなりうる (2010)
  • Author(s): 内海健、天本理恵、康東天
  • Organizer: 第83回日本分子生物学会神戸ポートアイランド
  • Place of Presentation: 神戸
• [Presentation] Mitochondrial p32 is highly expressed in prostate cancer and is associated with PSA relapse time after prostatectomy (2010)
  • Author(s): Takeshi Uchiumi, Rie Amamoto, Yoshinao Oda, Masasumi Tsuneyoshi, Akira Yokomizo, Seiji Naito, Yoohyun Song
  • Organizer: 第69回日本癌学会大阪国際会議場
  • Place of Presentation: 大阪
• [Presentation] Role of ZNF143 in tumor growth through transcriptional regulation of DNA replication and cell cycle associated genes (2010)
  • Author(s): Masaki Akiyama, Hiroto Izumi, Eiji Kashiwagi, Yoshihiro Yasuniwa, Bin Han, Ying Wu, Takeshi Uchiumi, Tokuzou Arao, Kazuto Nishio, Kimitoshi Kohno
  • Organizer: 第69回日本癌学会大阪国際会議場
  • Place of Presentation: 大阪
• [Presentation] ミトコンドリア蛋白p32は前立腺がんの予後マーカーになる (2010)
  • Author(s): 内海健、康東天
  • Organizer: 第57回日本臨床検査医学会東京
  • Place of Presentation: 京王プラザホテル
• [Presentation] Mitochondrial p32 is highly expressed in prostate cancer and is associated with shorter PSA relapse time after prostatectomy (2010)
  • Author(s): Takeshi Uchiumi, Rie Amamoto, Dongchon Kang
  • Organizer: The 7th Conference of Asian Society for Mitochondrial Research and Medicine(ASMRM) The 10th Conference of Japanese Society of Mitochondrial reaserch and Medicine(J-Mit) Fukuoka International Congress Center
  • Place of Presentation: Fukuoka
• [Presentation] The expression of ubiquitous mitochondrial creatine kinase is downregulated in prostate cancer progression (2010)
  • Author(s): Takeshi Uchiumi, Rie Amamoto, Yoohyun Song, Yoshinao Oda, Masasumi Tsuneyoshi, Akira Yokomizo, Seiji Naito
  • Organizer: 第70回日本癌学会名古屋国際会議場
  • Place of Presentation: 名古屋
• [Presentation] Downregulation of PDE4B activates protein kinase A and contributes to the progression of prostate cancer (2010)
  • Author(s): Eiji Kashiwagi, Mashaki Shiota, Akira Yokomizo, Junichi Inokuchi, Takeshi Uchiumi, Seiji Naito
  • Organizer: 第70回日本癌学会名古屋国際会議場
  • Place of Presentation: 名古屋
• [Presentation] ミトコンドリア蛋白p32は前立腺がんの予後マーカーとなりうる (2010)
  • Author(s): 内海健, 康東天
  • Organizer: 第57回 日本臨床検査医学会
  • Place of Presentation: 東京
• [Presentation] The mitochondrial function and cell growth of mitochondrial translation related protein (2009)
  • Author(s): Takeshi Uchiumi, Dongchon Kang
  • Organizer: 第32回日本分子生物学会パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] Effects of overexpression of mitochondrial transcription factor A on mitochondrial genome in Drosophila melanogaster (2009)
  • Author(s): Chika Tsumita, Takeshi Uchiumi, Dongchon Kang, Etsuko T. Matsuura積田知佳、内海健、康東天、松浦悦子
  • Organizer: 第32回日本分子生物学会パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] Mitochondrial translation related protein is involved in cancer cell growth and cell cycle (2009)
  • Author(s): Takeshi Uchiumi
  • Organizer: 第68回日本癌学会パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] The role of YB-1, a binding protein partner of NPM, in hematopoiesis and acute myeloid leukemia (2009)
  • Author(s): Yoko Ogasawara, Takuo Katsumoto, Takeshi Uchiumi, Kimitoshi Kohno, Issay Kitabayashi小笠原陽子、勝本拓夫、内海健,河野公俊、北林一生
  • Organizer: 第68回日本癌学会パシフィコ横浜
  • Place of Presentation: 横浜
• [Presentation] がんにおけるミトコンドリア翻訳因子ERAL1の機能 (2009)
  • Author(s): 内海健、康東天一般口演
  • Organizer: 第56回日本臨床検査医学会札幌
  • Place of Presentation: 札幌コンベンションセンター
• [Presentation] ワークショップ口演ミトコンドリアDNA維持制御因子とがん (2009)
  • Author(s): 内海健、康東天
  • Organizer: 第49回日本臨床化学会
  • Place of Presentation: 長崎大学、長崎
• [Presentation] ミトコンドリアDNA維持制御因子とがん (2009)
  • Author(s): 内海健, 康東天
  • Organizer: 第49回 日本臨床化学会
  • Place of Presentation: 長崎
• [Presentation] がんにおけるミトコンドリア翻訳因子ERAL1の機能 (2009)
  • Author(s): 内海健, 康東天
  • Organizer: 第56回 日本臨床検査医学会
  • Place of Presentation: 札幌
• [Presentation] The knockdown of ERAL1 is involved in assembly of mitochondrial ribosome (2009)
  • Author(s): 内海健, 康東天
  • Organizer: 第9回日本ミトコンドリア学会
  • Place of Presentation: 東京
• [Presentation] The knockdown of ERAL1 is involved in assembly of mitochondrial ribosome
  • Author(s): Takeshi Uchiumi, Dongchom Kang
  • Organizer: 第9回日本ミトコンドリア学会
  • Place of Presentation: 東京大学鉄門記念講堂、東京