Although several lines of evidence have implicated mitochondrial dysfunction in cancer aetiology, it is still unclear how and to what extent the dysregulation of mitochondrial function contributes to the behaviour of cancer cell. Today I will present some recent results obtained using a cell model with defined levels of mitochondrial DNA mutation, mTUNE, to investigate the direct consequences of mitochondrial dysfunction. We found that impaired utilization of reduced nicotinamide adenine dinucleotide (NADH) by the mitochondrial respiratory chain leads to cytosolic reductive carboxylation of glutamine as a new mechanism for cytosol-confined NADH recycling supported by malate dehydrogenase 1 (MDH1). We also observed that increased glycolysis in cells with mitochondrial dysfunction is associated with increased cell migration in an MDH1-dependent fashion. Our results elucidate a novel link between mitochondrial dysfunction and cancer metabolism, associated with changes in cell behaviour.
Video from the Keynote Speaker Dr. Christian Frezza can be found as below: