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Suhane 2013 Bio Open

From Bioblast
Publications in the MiPMap
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 2:295-305.

» PMID: 23519235 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 “metabolic threshold” for the observation of aerobic glycolysis phenotype within the confines of mitochondrial dysfunction. Keywords: Mitochondrial complex I, NDUFS3, Metabolic switch, Aerobic glycolysis, Reactive oxygen species, Mitochondrial dysfunction


Labels: MiParea: Respiration  Pathology: Cancer  Stress:Oxidative stress;RONS 

Tissue;cell: HEK 

Enzyme: Complex I  Regulation: Aerobic glycolysis, Flux control, Substrate 

Pathway: