Kyushu University Academic Staff Educational and Research Activities Database
Researcher information (To researchers) Need Help? How to update
YASUKAWA TAKEHIRO Last modified date:2020.01.10

Assistant Professor / Department of Clinical Chemistry and Laboratory Medicine
Department of Basic Medicine
Faculty of Medical Sciences




E-Mail
Homepage
http://www.cclm2.med.kyushu-u.ac.jp/mitochondria_toppage_EN_2014.html
Academic Degree
Doctor of Engineering [conferred by The University of Tokyo]
Field of Specialization
Molecular Biolodgy, Mitochondria, Mitochondrial DNA
Outline Activities
In my five years graduate studies at the University of Tokyo, Japan, I made a contribution to advance our understanding on the molecular pathogenesis of human mitochondrial disease with mutations in mitochondrial transfer RNA genes encoded on mitochondrial DNA. After conferment of a doctoral degree in 2002, I conducted my postdoctoral research at Medical Research Council in Cambridge, UK for five and a half years and contributed to the cutting-edge research on the mechanism of mammalian mitochondrial DNA replication (2002-2007). Then, I continued my research on mitochondrial DNA as a principal investigator at University College London, UK with a BBSRC David Phillips Fellowship for 5 years (2007-2012). In Nov. 2012, I took up an assistant professor position at Department of Clinical Chemistry and Laboratory and started a couple of exciting projects on the replication and maintenance of mammalian mitochondrial DNA.
Research
Research Interests
  • Mitochondrial genome, Mitochondria, DNA replication, DNA maintenance
    keyword : mitochondria, mitochondrial DNA, DNA replication
    2012.11~2020.03.
Academic Activities
Reports
1. Yasukawa, T.*, Kang, D. [*corresponding author], An overview of mammalian mitochondrial DNA replication mechanisms, J. Biochem., doi.org/10.1093/jb/mvy058, 64(3):183–193, 2018.06.
2. Yasukawa, T., Poulton, J., Mitochondrial DNA Replication, Royal Society of Chemistry (London), Chapter 11 in Molecular Themes in DNA Replication (pp.316-345), 2009.10.
3. Yasukawa, T., Suzuki, T., Ohta, S., Watanabe, K., Wobble modification defect suppresses translational activity of tRNAs with MERRF and MELAS mutations, Mitochondrion, 2, 129-141, 2002.02.
Papers
1. Matsuda S, Yasukawa T*, Sakaguchi S, Ichiyanagi K, Unoki M, Gotoh K, Fukuda K, Sasaki H, Suzuki T, Kang D., Accurate estimation of 5-methylcytosine in mammalian mitochondrial DNA, Sci. Rep., 8, 5801, [*corresponding author], 2018.04.
2. Moss, C.F., Dalla Rosa, I., Hunt, L.E., Yasukawa, T., Young, R., Jones, A.W.E., Reddy, K., Desai, R., Virtue, S., Elgar, G., Voshol, P., Taylor, M.S., Holt I.J., Reijns, M.A.M., Spinazzola, A., Aberrant ribonucleotide incorporation and multiple deletions in mitochondrial DNA of the murine MPV17 disease model, Nucleic Acids Res., 45, 22, 12808-12815, 2017.11, All DNA polymerases misincorporate ribonucleotides
despite their preference for deoxyribonucleotides,
and analysis of cultured cells indicates
that mammalian mitochondrial DNA (mtDNA) tolerates
such replication errors. However, it is not clear
to what extent misincorporation occurs in tissues,
or whether this plays a role in human disease.
Here, we show that mtDNA of solid tissues contains
many more embedded ribonucleotides than that
of cultured cells, consistent with the high ratio of
ribonucleotide to deoxynucleotide triphosphates
in tissues, and that riboadenosines account for
three-quarters of them. The pattern of embedded
ribonucleotides changes in a mouse model of Mpv17
deficiency, which displays a marked increase in
rGMPs in mtDNA. However, while the mitochondrial
dGTP is low in the Mpv17?/? liver, the brain shows
no change in the overall dGTP pool, leading us
to suggest that Mpv17 determines the local concentration
or quality of dGTP. Embedded rGMPs
are expected to distort the mtDNA and impede its
replication, and elevated rGMP incorporation is
associated with early-onset mtDNA depletion in
liver and late-onset multiple deletions in brain of
Mpv17?/? mice. These findings suggest aberrant
ribonucleotide incorporation is a primary mtDNA
abnormality that can result in pathology..
3. Akman, G., Desai, R., Bailey, L.J., Yasukawa, T., Dalla Rosa, I., Durigon, R., Holmes, J.B., Moss, C.F., Mennuni, M., Houlden, H., Crouch, R.J., Hanna, M.G., Pitceathly, R.D., Spinazzola, A., Holt I.J., Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria, Proc. Natl. Acad. Sci. USA., 113, 30, E4276-E4285, 2016.07, The genetic information in mammalian mitochondrial DNA is denselypacked; there are no introns and only one sizeable noncoding, orcontrol, region containing key cis-elements for its replication andexpression. Many molecules of mitochondrial DNA bear a thirdstrand of DNA, known as “7S DNA,” which forms a displacement(D-) loop in the control region. Here we show that many other moleculescontain RNA as a third strand. The RNA of these R-loops mapsto the control region of the mitochondrial DNA and is complementaryto 7S DNA. Ribonuclease H1 is essential for mitochondrial DNAreplication; it degrades RNA hybridized to DNA, so the R-loop is apotential substrate. In cells with a pathological variant of ribonucleaseH1 associated with mitochondrial disease, R-loops are of lowabundance, and there is mitochondrial DNA aggregation. These findingsimplicate ribonuclease H1 and RNA in the physical segregationof mitochondrial DNA, perturbation of which represents a previouslyunidentified disease mechanism..
4. Qu, J., Yasukawa, T.*, Kang, D., Suppression of mitochondrial transcription initiation complexes changes the balance of replication intermediates of mitochondrial DNA and reduces 7S DNA in cultured human cells, J. Biochem., doi:10.1093/jb/mvw010, [*corresponding author], 2016.02, [2017年日本生化学会JB論文賞受賞].
5. Reyes, A., Kazak, L., Wood, S.R., Yasukawa, T., Jacobs, H.T., Holt I.J., Mitochondrial DNA replication proceeds via a ‘bootlace’ mechanism involving the incorporation of processed transcripts, Nucleic Acids Res., 10.1093/nar/gkt196, 41(11):5837-5850, 2013.06.
6. Ruhanen, H., Ushakov, K., Yasukawa, T.* [*corresponding author], Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells, Biochim. Biophys. Acta, 1813, 2000-2007, 2011.12.
7. Ruhanen, H., Borrie, S., Szabadkai, G., Tyynismaa, H., Jones, A. W. E., Kang, D., Taanman, J.-W., Yasukawa, T.* [*corresponding author], Mitochondrial single-stranded DNA binding protein is required for maintenance of mitochondrial DNA and 7S DNA but is not required for mitochondrial nucleoid organization, Biochim. Biophys. Acta, 1803, 931-939, 2010.08.
8. Yasukawa, T., Reyes, A., Cluett, T. J., Yang, M. Y., Bowmaker, M., Jacobs, H. T., Holt, I. J., Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand, EMBO J., 25, 5358-5371, 2006.10.
9. Yasukawa, T., Yang, M. Y., Jacobs, H. T., Holt, I. J., A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA, Mol. Cell, 18, 651-662, 2005.06.
10. Yasukawa, T., Suzuki, T., Ishii, N., Ohta, S., Watanabe, K., Wobble modification defect in tRNA disturbs codon-anticodon interaction in a mitochondrial disease, EMBO J., 20, 4794-4802, 2001.09.
Presentations
1. Takehiro Yasukawa, Shigeru Matsuda, Yuriko Sakaguchi, Kenji Ichiyanagi, Motoko Unoki, Kazuhito Gotoh, Kei Fukuda, Hiroyuki Sasaki, Tsutomu Suzuki, Dongchon Kang, Epigenetic feature of mitochondrial DNA, The 16th Conference of Asian Society for Mitochondrial Research and Medicine [ASMRM]& The 19th Conference of Japanese Society of Mitochondrial Research and Medicine[J-mit], 2019.10.
2. Takehiro Yasukawa, Shigeru Matsuda, Yuriko Sakaguchi, Kenji Ichiyanagi, Motoko Unoki, Kazuhito Gotoh, Kei Fukuda, Hiroyuki Sasaki, Tsutomu Suzuki, Dongchon Kang , Epigenetic control and mitochondrial DNA methylation, UMDF Mitochondrial Medicine 2019 , 2019.06.
3. Takehiro Yasukawa, Shigeru Matsuda, Yuriko Sakaguchi, Kenji Ichiyanagi, Motoko Unoki, Kazuhito Gotoh, Kei Fukuda, Hiroyuki Sasaki, Tsutomu Suzuki, Dongchon Kang , Accurate estimation of 5-methylcytosine in mammalian mitochondrial DNA, The 1st International Mitochondria Meeting for Young Scientists, 2018.04.
Membership in Academic Society
  • The Molecular Biology Society of Japan
  • The Japanese Society of Mitochondrial Research and medicine
Educational
Educational Activities
Supervision of master course and PhD course students in the laboratory. / Lectures to undergraduate and graduate students.
Social
Professional and Outreach Activities
I held a JSPS Bilateral Joint Research Seminar as a leading scientist at Helsinki (Finland) with Japanese and Finnish researchers in Oct 2015. .