IDH1 and cancer: Although Otto Warburg proposed that cancer is a disease of dysfunctional mitochondria back in 1956, this hypothesis has been scrutinised over the subsequent years.41 Genetic mutations in key mitochondrial enzymes of the Krebs cycle, such as succinate dehydrogenase (SDH), fumarate hydratase (FH) and IDH1/2, have recently been identified as cancer initiators.