Autochtone regulation of mitochondrial transcription by DNA-Topoisomerase 1mt

During evolution, mitochondria have transferred most of their genome to the cell nucleus. Just a few key components of the respiratory chain have remained under the control of the mitochondrial genome (mtDNA). Current belief holds that these genes have been retained to allow for autochtone adaptation of respiratory capacity to the local REDOX-state. We have observed that the enzyme DNA-Topoisomerase 1mt (TOP1MT) regulates mitochondrial transcription via altering mtDNA-supercoiling. Given that TOP1MT is REDOX-sensitive, the enzyme could provide the so far elusive mechanism of lokal REDOX-Regulation of mtDNA-transcription.

  1. Sobek, S. and Boege, F. (2014) DNA topoisomerases in mtDNA maintenance and ageing. Experimental gerontology, 56, 135-141.
  2. Kalfalah, F., Sobek, S., Bornholz, B., Gotz-Rosch, C., Tigges, J., Fritsche, E., Krutmann, J., Kohrer, K., Deenen, R., Ohse, S. et al. (2014) Inadequate mito-biogenesis in primary dermal fibroblasts from old humans is associated with impairment of PGC1A-independent stimulation. Experimental gerontology, 56, 59-68.
  3. Sobek, S., Dalla Rosa, I., Pommier, Y., Bornholz, B., Kalfalah, F., Zhang, H., Wiesner, R.J., von Kleist-Retzow, J.C., Hillebrand, F., Schaal, H. et al. (2013) Negative regulation of mitochondrial transcription by mitochondrial topoisomerase I. Nucleic Acids Res, 41, 9848-9857.
  4. Dalla Rosa, I., Goffart, S., Wurm, M., Wiek, C., Essmann, F., Sobek, S., Schroeder, P., Zhang, H., Krutmann, J., Hanenberg, H. et al. (2009) Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA. Nucleic Acids Res, 37, 6414-6428.

Funded by DFG (Bo910/10-1).

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