A Mechanism for Mitochondrial DNA Copy Number-regulated Simultaneous Expression of Proteins in Respiratory Complexes.

• Project/Area Number: 23510237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Genome biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: LING Feng 独立行政法人理化学研究所, 吉田化学遺伝学研究室, 専任研究員 (70281665)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 出芽酵母 / DNA組換え / ミトコンドリアDNA / ミトコンドリア融合 / 酸化ストレス応答 / ローリングサークル型複製 / DNA損傷 / Mhr1タンク質 / コンカテマー / DNA二本鎖切断 / 呼吸鎖複合体 / ミトコンドリア / ローリングサークル型DNA複製 / ミトコンドリアヌクレアーゼ / Saccharomyces cerevisiae / mitochondrial fusion / replication / zygote / Concatemer / Rolling-circle type / 遺伝学 / 遺伝子 / 核酸 / ストレス / 品質管理 / DNA複製

Research Abstract

We found that mitochondrial fusion induces dissociation of Complex V of the respiratory chain and ROS generation, which increases mitochondrial DNA (mtDNA) copy number in a manner dependent on the homologous DNA pairing protein Mhr1 and also increases in the mtDNA-encoded subunits of Complex V. These results suggested that activation of recombination-dependent replication during mitochondrial fusion plays important roles in maintenance of mitochondrial genomes by preventing generation of mitochondria lacking mtDNA. We further uncovered a mechanism in which relative expression levels of the DNA damage inducible protein Din7 to Mhr1 determine the choice of replication or repair after pairing of homologous DNA by Mhr1.

Research Products

• [Journal Article] Din7 and Mhr1 expression levels regulate double-strand-break-induced replication and recombination of mtDNA at ori5 in yeast (2013)
  • Author(s): Feng Ling, Akiko Hori, Ayako Yoshitani, Rong Niu, Minoru Yoshida, and Takehiko Shibata
  • Journal Title: Nucleic Acids Research Pages: 5799-5816
  • Peer Reviewed
• [Journal Article] Din7 and Mhr1 expression levels regulate double-strand-break–induced replication and recombination of mtDNA at ori5 in yeast (2013)
  • Author(s): Feng Ling, Akiko Hori, Ayako Yoshitani, Rong Niu, Minoru Yoshida and Takehiko Shibata,
  • Journal Title: Nucleic Acids Research Volume: 41 (11) Pages: 5799-5816
  • Peer Reviewed
• [Journal Article] Din7 and Mhr1 expression levels regulate double-strand-break-induced replication and recombination of mtDNA at ori5 in yeast (2013)
  • Author(s): *Feng Ling, Akiko Hori, Ayako Yoshitani, Rong Niu, Minoru Yoshida and Takehiko Shibata
  • Journal Title: Nucleic Acids Research Volume: 41(8) Issue: 11 Pages: 5799-5816
  • DOI: 10.1093/nar/gkt273
  • Peer Reviewed
• [Journal Article] Mitochondrial fission proteins Fis1 and Mdv1, but not Dnm1, play a role in maintenance of heteroplasmy in budding yeast (2012)
  • Author(s): Elliot Bradshaw, Minoru Yoshida and Feng Ling
  • Journal Title: FEBS Letters Volume: 586(8) Pages: 1245-1251
  • Peer Reviewed
• [Journal Article] Increased 4977-bp deletion in mitochondrial DNA upon ATM/Chk2 checkpoint activation in HeLa cells (2012)
  • Author(s): Rong Niu, Minoru Yoshida and Feng Ling
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Increases in Mitochondrial DNA Content and 4977-bp Deletion Upon ATM/Chk2 Checkpoint Activation in HeLa Cells (2012)
  • Author(s): Rong Niu, Minoru Yoshida and *Feng Ling
  • Journal Title: PLoS ONE Volume: 7(7)
  • Peer Reviewed
• [Journal Article] Mitochondrial fusion increases the mitochondrial DNA copy number in budding yeast (2011)
  • Author(s): Akiko Hori, Minoru Yoshida and Feng Ling
  • Journal Title: Genes to Cells Volume: 16 Pages: 527-544
  • Peer Reviewed
• [Journal Article] Gene conversion through double-strand break-induced DNA replication and mitochondrial homoplasmy (2011)
  • Author(s): Feng Ling, Tsutomu Mikawa and Takehiko Shibata
  • Journal Title: Genes Volume: 2 Pages: 169-190
  • Peer Reviewed
• [Journal Article] Enlightenment of yeast mitochondrial homoplasmy : diversified roles of gene conversion (2011)
  • Author(s): Ling, F., Mikawa, T. and Shibata, T.
  • Journal Title: Genes (Basel) Volume: 2 Issue: 1 Pages: 169-190
  • DOI: 10.3390/genes2010169
  • Peer Reviewed
• [Presentation] 健全な iPS 細胞樹立に向けたミトコンドリア病患者細胞の mtDNA ホモプラスミー化促進法の開発 (2014)
  • Author(s): 凌楓、牛栄、柴田武彦、吉田稔、畠山英之、後藤雄一
  • Organizer: CREST/さきがけ/JST-CIRM 合同シンポジウム
  • Place of Presentation: 東京都江東区青海2-3-6 日本科学未来館
  • Year and Date: 2014-01-15
• [Presentation] A Novel Mechanism for Mitochondrial DNA Inheritance and its Medical Significance (2012)
  • Author(s): Feng Ling
  • Organizer: Mitochondrial Genetics Forum at Peking University
  • Place of Presentation: Peking University First Hospital, Xi-shi-ku St, Beijing 100034, China
  • Year and Date: 2012-08-29
• [Presentation] Role of Recombination-mediated Replication in Mitochondrial Inheritance (2012)
  • Author(s): Feng Ling
  • Organizer: The Glycobiology Forum at Jiang Nan University
  • Place of Presentation: School of Biotechnology, Jiangnan University, No. 188800 Lihu Avenue, Wuxi, Jiangsu, P. C. 214122, China
  • Year and Date: 2012-07-10
• [Presentation] Recombination-mediated Replication in Mitochondrial DNA Inheritance (2012)
  • Author(s): Feng Ling, Rong Niu, Eliot Bradshaw, Minoru Yoshida
  • Organizer: Global Conference of Chinese Geneticists
  • Place of Presentation: Zhejiang University in Hangzhou, Zhejiang Province, China
• [Presentation] A Novel Mechanism for Mitochondrial Inheritance & Its Biomedical Importance (2012)
  • Author(s): Feng Ling
  • Organizer: Symposium of Mitochondral Biomedicine
  • Place of Presentation: Zhejiang University in Hangzhou, Zhejiang Province, China
• [Presentation] Recombination-mediated Replication in Mitochondrial DNA Inheritance (2012)
  • Author(s): ○Feng Ling, Rong Niu, Eliot Bradshaw, Minoru Yoshida
  • Organizer: Global Conference of Chinese Geneticists,
  • Place of Presentation: Zhejiang University in Hangzhou, Zhejiang Province, China
  • Invited
• [Presentation] 健全なiPS細胞樹立に向けたミトコンドリア病患者細胞のmtDNAホモプラスミー化促進法の開発
  • Author(s): 凌楓、牛栄、柴田武彦、吉田稔、畠山英之、後藤雄一
  • Organizer: CREST/さきがけ/JST-CIRM 合同シンポジウム
  • Place of Presentation: 東京都江東区青海2-3-6 日本科学未来館
• [Presentation] Role of Recombination-mediated Replication in Mitochondrial Inheritance
  • Author(s): Feng Ling
  • Organizer: The Glycobiology Forum at Jiang Nan University, School of Biotechnology, Jiangnan University,
  • Place of Presentation: No. 188800 Lihu Avenue, Wuxi, Jiangsu, P.C. 214122, China
  • Invited
• [Presentation] A Novel Mechanism for Mitochondrial DNA Inheritance and its Medical Significanc
  • Author(s): Feng Ling
  • Organizer: Mitochondrial Genetics Forum at Peking University
  • Place of Presentation: Peking University First Hospital, Xi-shi-ku St, Beijing 100034, China
  • Invited