Does metabolic plasticity maintain proliferation in pyruvate dehydrogenase deficient cells?
Although PDH suppression substantially alters central carbon metabolism, the data indicate that rapid cell proliferation occurs independently of PDH activity. Our findings reveal that this central enzyme is essentially dispensable for growth and proliferation of both primary cells and established cell lines. We also identify the compensatory mechanisms that are activated under PDH deficiency, namely scavenging of extracellular lipids and lipogenic acetyl-CoA production from reductive glutamine metabolism through IDH1.
Our findings demonstrate that the Akt/mTOR pathway is upregulated in OVC, indicating a role for this pathway in the development and progression of this malignancy.