Suhane 2013 Bio Open
Suhane S, Kanzaki H, Arumugaswami V, Murali R, VK (2013) Mitochondrial NDUFS3 regulates the ROS-mediated onset of metabolic switch in transformed cells. Bio Open 0:01-11. |
Β» doi: 10.1242/bio.20133244 Open Access
Suhane S, Kanzaki H, Arumugaswami V, Murali R, VK (2013) Bio Open
Abstract: Aerobic glycolysis in transformed cells is an unique metabolic phenotype characterized by a hyperactivated glycolytic pathway even in the presence of oxygen. It is not clear if the onset of aerobic glycolysis is regulated by mitochondrial dysfunction and, if so, what the metabolic windows of opportunity available to control this metabolic switch (mitochondrial to glycolytic) landscape are in transformed cells. Here we report a genetically-defined model system based on the gene-silencing of a mitochondrial complex I subunit, NDUFS3, where we demonstrate the onset of metabolic switch in isogenic human embryonic kidney cells by differential expression of NDUFS3. By means of extensive metabolic characterization, we demonstrate that NDUFS3 gene silencing systematically introduces mitochondrial dysfunction thereby leading to the onset of aerobic glycolysis in a manner dependent on NDUFS3 protein levels. Furthermore, we show that the sustained imbalance in free radical dynamics is a necessary condition to sustain the observed metabolic switch in cell lines with the most severe NDUFS3 suppression. Together, our data reveal a novel role for mitochondrial complex I subunit NDUFS3 in regulating the degree of mitochondrial dysfunction in living cells, thereby setting a βmetabolic thresholdβ for the observation of aerobic glycolysis phenotype within the confines of mitochondrial dysfunction. β’ Keywords: Mitochondrial complex I, NDUFS3, Metabolic switch, Aerobic glycolysis, Reactive oxygen species, Mitochondrial dysfunction
Labels: MiParea: Respiration
Pathology: Cancer
Stress:Oxidative stress;RONS
Enzyme: Complex I Regulation: Aerobic glycolysis, Flux control, Substrate;glucose;TCA cycle"Substrate;glucose;TCA cycle" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.