Although this effect is mainly considered a response/feedback mechanism to lack of oxygen during tumor development, further research has revealed that this process can be responsible for tumor initiation through a series of distinct mutations in genes encoding mitochondrial metabolic enzymes: succinate dehydrogenase (SDH), isocitrate dehydrogenase (IDH), and fumarate-hydratase (FH). The gene discussed is IDH3A; the disease is neoplasm.