Fig. 4: Nuclear IDH-2 induces an anti-apoptotic effect.
From: Nuclear translocation of mitochondrial dehydrogenases as an adaptive cardioprotective mechanism
a α-KG levels measured in isolated nuclei, n = 3 p value* <0.0130. b Schematic of the proposed α-KG-AMPK-Sirtuin- pathway. c Western blots showing increased AMPK phosphorylation upon nuclear IDH-2 expression. ß-actin was used as a loading control. d Sirtuin activity represented as OD/min/mg. n = 3 P value** = 0.0036. e Schematic of inhibitory sites of compound C and sirtinol in the α-KG-AMPK-Sirtuin pathway. f, g Caspase 9 activity (f) n = 3 p value* <0.05, p value*** = 0.0002, p value **** <0.0001, and cell death (g) n = 4 p value*** <0.0005, p value** = 0.0085 upon inhibition of AMPK and sirtuin by compound C and sirtinol, respectively. h Reduced gene expression of anti-apoptotic protein BCL2 by AMPK and sirtuin inhibition in cells expressing nuclear IDH-2. n = 3 p value** <0.05, p value* <0.002. i, j Annexin V staining in iPSC-CM expressing nuclear IDH-2 and treated with succinate in the presence of DRN (i) or expressing IDH-2 mutants in the nuclei of cells treated with DRN (j). n = 3 P value**** <0.0001.
