| dc.description.abstract | The Warburg effect is the most common altered metabolism phenotype in cancer and is characterised by the increase in lactate production through aerobic glycolysis. There are several proposed functions of the Warburg effect in tumours: rapid ATP synthesis, accumulation of intermediates, and regeneration of NAD+. Metabolism and cell cycle regulates each other and when there is a disturbance, such as altered levels of the redox pair NAD+/NADH, it can lead to chromosomal instability (CIN). Until now, the relationship between aerobic glycolysis and CIN has not fully been established. To answer this question, we will attempt to induce the Warburg effect in non cancerous cells through chemical activation, LDHB phosphomimicking, and disturbing mitochondrial respiration with knockouts. To
monitor metabolite changes on a chromatin level, we used fluorescent based genetic encoded reporter. To resolve glycolytic function in cells, we utilised the Seahorse bioenergetic profiling technique. We could not induce glycolysis with the drugs: AOAA, TEPP-46, and GSK2837808A, and LDHB phosphomimicking. We perturbed mitochondrial respiration by MDH1, SLC25A12/13, MDH2, and PDH1 knockouts (KO) and found increased lactate formation with MDH1, MDH2, and PDH1 KO. Strikingly, we discovered that the most glycolytic line– MDH2 KO, exhibited the greatest population of micronuclei. Together, these results show a positive correlation between glycolytic level and CIN occurrence. | |
