Mitochondrial DNA and its damage and repair in cancer

Teams of researchers from the Institute of Biotechnology led by prof. Jiri Neuzil and the Institute of Experimental Medicine led by dr. Pavel Vodicka and dr. Sona Vodenkova recently published a review paper in the highly acclaimed journal Trends in Cancer, focusing under the title of Mitochondrial DNAdamage, repair and replacement.

The authors focus in this paper on the role of mitochondria DNA (mtDNA) in the origin of tumours and in their gowth. They mention, beside others, a remarkable discovery when swaping mtDNA between metastatic and non-metastatic breast cancer cells, resulting in a corresponding switch of metastatic properties. They point to the important role of mtDNA, whose aberrations affect the process of carcinogenesis in spite of the fact that it codes only for 13 polypeptides (all of which are components of oxidative phosphorylation), while nuclear DNA encodes tens of thousands of proteins. They describe in detail the bases for increased susceptibility of mtDNA to mutagens, a reason why it is more sensitive to damage, and they also provide the ground for repair mechanisms of mtDNA, which are not well understood, compared to those of nuclear DNA. Further, they propose horizontal mitochondrial transfer as a new mode of mtDNA repair by means of its replacement with healthy mtDNA via its transfer using bridges between cancer cells and cells of the tumour stroma.

Figure: The Scheme of possible types of mtDNA damage and its repair mechanisms

This review paper is a prime example of collaboration of laboratories from two institutes of the Academy of Science of the Czech Republic, which is supported by an EXPRO grant from the Czech Science Foundation.

More information: https://www.cell.com/trends/cancer/abstract/S2405-8033(24)00212-7