Increased susceptibility of mitochondrial subpopulations to diabetic cardiomyopathy associated dysfunction

Cardiomyopathy is recognized as a major contributor to the morbidity and mortality associated with diabetes, and mitochondrial dysfunction may play a central role in its etiology. We examined the influence of diabetic (D) cardiomyopathy on mitochondrial function and oxidative stress using streptozotocin‐treated and control (C) mice. Activities of electron transport chain (ETC) complexes I, III, and IV were significantly decreased in D heart mitochondria as compared to C ( P <0.05, all three). Reactive oxygen species (ROS) generation was significantly increased in D heart homogenate as compared to C ( P <0.05). Heart mitochondria from D mice possessed a two‐fold greater ROS content as compared to C ( P <0.05). Oxidatively‐modified proteins in total heart homogenate were significantly greater in D vs. C. To identify specific loci of mitochondrial dysfunction, we examined oxidatively‐modified proteins in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial subpopulations. D SS and IMF mitochondria possessed greater protein oxidation contents than C. D increased protein oxidation products in the IMF to a greater extent, than in SS. These results indicate that diabetes enhances cardiac mitochondrial dysfunction due in part to increased ROS and oxidative stress. Further, IMF mitochondria may be more susceptible to oxidative stress associated with diabetic cardiomyopathy. (Supported by AHA 0665237B)