IDH2 and heart failure: Therefore, under conditions of oxidative stress, as in the presence of rotenone in our experiments or with a functional block at complex I as reported for heart failure [11], ROS-mediated aconitase inactivation might further limit the flux of substrates into IDH and α-KGDH and thereby, further compromise mitochondrial antioxidative capacity, eliciting an adverse feed-forward mechanisms of mitochondrial oxidative stress.