Olivier Morel Morel
We found that the highly metabolically active phenotype is promoted by the overexpression of the mitochondrial enzyme Succinate Dehydrogenase (SDHA), which is particularly common in ovarian cancer. Prior research has examined succinate dehydrogenase insufficiency in a few uncommon diseases. There is still a need for more study because it has never been done how SDHA overexpression affects ovarian cancer metabolism. We looked into the effects of SDHA overexpression in ovarian cancer on its functional properties. We investigated the protein content of the metabolic pathways, cell proliferation, anchorage-independent growth, mitochondrial respiration, glycolytic activity, and ATP production rates in those cells using proteomics techniques and biological experiments. Last but not least, we ran a pharmacological screening to find medicines that selectively target tumor cells that overexpress SDHA. We demonstrated that cells overexpressing SDHA have improved energy metabolism and rely on both glycolysis and oxidative phosphorylation to provide the energy they require. Additionally, cells with a high SDHA phenotype were more susceptible to glucose and glutamine deprivation, which significantly decreased ATP output. We also discovered the antimetabolic substance shikonin, which exhibits strong activity against ovarian cancer cells overexpressing SDHA. The findings highlight the underappreciated function of SDHA in the metabolic reprogramming of ovarian cancer, opening up new treatment possibilities.