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

线粒体被称为细胞的动力室，因此它们产生细胞过程所需的能量。因此，线粒体功能或线粒体DNA中的畸变可对疾病（包括癌症）的发病机制具有直接影响。迄今为止，尽管线粒体DNA中的许多突变与癌症有关，但对线粒体DNA突变引起肿瘤的确切方式知之甚少。为了进一步研究这一点，我们分析了230个参与修复DNA的基因，看看它们是否会影响线粒体DNA的水平。有趣的是，我们发现了3个以前与癌症相关的基因，它们可以调节线粒体DNA水平。我们还观察到，在这些基因耗尽后，细胞中参与能量产生途径的一些蛋白质的表达发生了变化。因此，这表明这些基因也可以改变线粒体的功能。在这项提案中，我们的目标是研究这些已鉴定的基因如何调节线粒体DNA的完整性，并确定这如何影响线粒体的功能。我们还将研究患者的肿瘤样本，以确定在缺乏这些基因的情况下线粒体DNA的水平。

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.