To determine whether IDH1 and IDH2 mutants can dominantly inhibit the activity of endogenous IDH1 and IDH2 enzymes, we assayed NADP+-IDH activity of lysates of HOG cells overexpressing IDH1-WT, IDH2-WT, or cancer-derived IDH1 R132 and IDH2 R172 mutants in the presence of 40 μM isocitrate. Here, IDH2 is linked to cancer.