Figure 7.

Metabolic alterations driven by IDH mutation in U251 cells. In cancer cells, glycolysis upregulation generates the production of reducing equivalents NADH, which is then shuttles from the cytosol to mitochondria with the MAS. Glutamine is converted to glutamate, which is further converted to αKG by GDH. IDH also produces αKG from isocitrate. In cells expressing IDH1^R132, IDH1^R132 converts αKG into D-2HG. To limit cellular αKG depletion, IDH1^R132-overexpressing cells diverts AAT from MAS function to produce αKG. As a result, glycolytic NADH is no longer fully imported into mitochondria. AAT, aspartate aminotransferase; ETC, electron transport chain; GDH, glutamate dehydrogenase; Gln, Glutamine; Glu, Glutamate; IDH, isocitrate dehydrogenase; LDH, lactate dehydrogenase; MAS, malate–aspartate shuttle; Pyr, pyruvate; TCA, tricarboxylic acid cycle