Characterization and impact of novel regulators of mitochondrial DNA integrity on tumourigenesis

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Mitochondria are the known as the power houses of the cell, such that they generate the energy required for cellular processes. Consequently, aberrations in mitochondrial function or in mitochondrial DNA can have direct implications on the pathogenesis of disease including cancer. To date, although many mutations in mitochondria DNA have been associated with cancer, there is little known about the exact way in which mitochondrial DNA mutations can give rise to tumours. To further investigate this, we analysed 230 genes involved in repairing DNA to see if they could influence the levels of mitochondrial DNA, when they were silenced. Interestingly, we identified 3 genes which were previously associated with cancer, that can regulate mitochondrial DNA levels. We also observed upon depletion of these genes, changes in expression of some of the proteins involved in the energy-generating pathways in the cell. Therefore suggesting that these genes can also alter the function of mitochondria. In this proposal, we aim to investigate how these identified genes can regulate mitochondrial DNA integrity and determine how this can affect how mitochondria function. We will also look at patient tumour samples to determine the level of mitochondrial DNA in the absence of some of these genes.