The genetics of keeping our cells powered up

Research led by the University of Sheffield is offering new insights into how we might treat some of the most devastating medical conditions, such as cancer and neurodegenerative disease.

Modern medical research has revealed much about how cells protect DNA, our biological instruction pack, in order to remain healthy. Most of this research has focussed on the DNA found in the cell’s nucleus. However, mitochondria, the power units of cells that generate energy needed for almost all cellular functions, contain their own DNA, and this DNA is at high risk of damage by the by-products of energy production. mito

How mitochondria ensure that the important biological instructions contained in their DNA remain undamaged is poorly understood. It is, however, critically important since maintaining mitochondrial DNA integrity is key in all aspects of cell function. If mitochondrial DNA is damaged, then there is an increased risk of cancer, neurodegenerative disease and other age-related disorders.

In an article published in Science Advances, an international group of scientists led by Professor Sherif El-Khamisy from the University of Sheffield has provided new insights into a novel repair pathway that controls how the mitochondrial DNA is read and processed, and how much oxygen the process requires. The results of the research have shown how the mitochondria is able to protect its DNA against damage caused by oxidative stress thereby keeping the cell healthy and functioning.

Professor El-Khamisy explained, “Such research as we have undertaken will benefit patients in the future as it offers insights into how we can develop personalised (precision) medicine.  

“This research offers us the chance, for example, to improve patient outcomes following partial liver transplantation, optimise the process of fertility treatment in the case of so-called three parent babies and develop new forms of cancer therapy by inhibiting tumour development.”

The researchers employed a biochemical and genetic approach to study the function of certain genes in cell and mouse models. Two key genes, TDP1 and TOP1, were found to play important roles in fixing structural faults and breaks in the mitochondrial DNA thus ensuring a healthy cell.

In a new collaboration with scientists at Manipal University in India, Professor El-Khamisy will address the link between the failure of cells to repair breaks in DNA and the development of neurodegenerative disease.

The Science Advances paper is available for download.

For further information, please contact: Professor Sherif El-Khamisy, Department of Molecular Biology and Biotechnology, University of Sheffield, 0114 222 2791,