Mitochondrial Dynamics in the Type 2 Diabetic Heart

Studies have shown that abnormal mitochondrial structure and function leads to cardiovascular disease in patients with type 2 diabetes (T2D). Mitochondrial dynamics (i.e. fusion and fission events) are normally occurring, and are the organelles response to environmental changes. Mitochondrial abnormalities in T2D may be associated with an imbalance of fusion and fission events. Fission leads to fragmented mitochondria which can be abnormally small, have fragmented cristae and thus be poor in ATP efficiency. Fission can also lead to larger reactive oxygen species (ROS) production. Fragmented mitochondria are cleared out of the cells by a process known as mitogphagy. Impaired mitophagy can lead to an accumulation of damaged mitochondria, thus leading to increased ROS production and inflammatory signals. We have previously demonstrated that the cocoa flavanol epicatechin provides cardioprotection in the setting of ischemia-reperfusion by reducing inflammation and ROS production. However the precise mechanisms are unknown. Using both in vivo and in vitro models of T2D, we will examine how epicatechin can regulate mitochondrial fusion/fission and mitophagy events. HL-1 cardiomyocytes will undergo glucolipotoxicity treatment, in which they will be cultured for 3 days in high glucose (~33 mM) and high fatty acids (0.6 mM) media in the absence or presence of epicatechin. Fluorescent microscopy, molecular, cellular, and biochemical techniques will be utilized to evaluate mitochondrial morphology and dynamics, and the cellular events leading to mitophagy. As the incidence of T2D rises, further investigation into possible therapies and treatments is warranted.