Dr. Takehiro Yasukawa, BBSRC David Phillips Fellow
- 020 7679 6613 / takehiro.yasukawa@ucl.ac.uk

Mitochondrial DNA Group

Lab summary

It is widely known that DNA resides in the nucleus.  Our body also contains indispensable ‘second genome’ which exists in one of the cellular organelles, mitochondria.  This genome is called “mitochondrial DNA”.

Mitochondria comprise a cellular compartment with many important functions.  They are often referred as the “powerhouse of the cell” as they produce energy to fuel the activities of the cell.  Interestingly, our mitochondria contain a small but indispensable DNA, the mitochondrial DNA.  While nuclear DNA exists at two copies per cell, mitochondrial DNA is a multicopy genome and is present typically at thousands copies per cell in the human body.  The structure, organisation and the mode of inheritance of mitochondrial DNA are distinct from those of nuclear DNA.  Abnormalities of mitochondrial DNA are associated with various human diseases and have been implicated in ageing. Understanding of the mechanisms involved in the maintenance of mitochondrial DNA is therefore of prime importance.

The Mitochondrial DNA group is interested in this fascinating genome and in the organelle in which it resides - the mitochondrion.  Our research question is “how do cells monitor, determine and regulate the copy number of mitochondrial DNA?”  We are investigating protein factors for the mtDNA maintenance and replication of mitochondrial DNA as well as the mechanistic details of replication.  We also focus on how energy demand and cellular status are communicated to mitochondria in order to manipulate the copy number.

We believe that studies of mitochondrial DNA and mitochondria will contribute to a better understanding of our health, ageing and diseases.

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Selected publications

Ruhanen H., Ushakov K., Yasukawa, T. (2011). Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA replication in cultured human cells. Biochim. Biophys. Acta - Molecular Cell Research, 1813, 2000-2007

Ruhanen, H., Borrie, S., Szabadkai, G., Tyynismaa, H., Jones, A. W. E., Kang, D., Taanman, J.-W., Yasukawa, T. (2010). 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

Yasukawa,T. & Poulton,J. (2009). Mitochondrial DNA Replication. Chapter 11 in Cox,L.S. (ed.) Molecular Themes in DNA Replication. London: Royal Society of Chemistry, 316-345. ISBN: 978-0-85404-164-0

Yasukawa T., Reyes A., Cluett T.J., Yang M.Y., Bowmaker M., Jacobs H.T. & Holt I.J. (2006) Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand. EMBO J. 25, 5358-5371. 

Yasukawa, T., Yang, M.Y., Jacobs, H.T. & Holt, I.J. (2005). A bidirectional origin of replication maps to the major non-coding region of human mitochondrial DNA. Mol. Cell 18, 651-662.

Yasukawa, T., Suzuki, T., Ishii, N., Ohta, S. & Watanabe, K. (2001). Wobble modification defect in tRNA disturbs codon-anticodon interaction in a mitochondrial disease. EMBO J. 20, 4794-4802.

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Academic Career

Funding

BBSRC

CRDC Research Funding from the UCLH Charities

University of London Central Research Fund Grant 2008/2009

JSPS funding of symposium scheme for Japanese researchers based in the UK (2011)

JSPS funding of symposium scheme for Japanese researchers based in the UK [PHASE2] (2012)