WEST VIRGINIA UNIVERSITY RESEARCH CORPORATION
One to two million people in the United States suffer from type 1 diabetes mellitus. Diabetic cardiomyopathy is an impairment of heart muscle that exists independently of coronary artery disease, and is associated with diabetes mellitus Diabetic cardiomyopathy is characterized by contractile dysfunction which contributes to myocardial infarction and heart failure. Hyperglycemia associated with diabetes mellitus, increases reactive oxygen species (ROS) generation. Because the mitochondrion is the primary site for ROS generation, determination of how mitochondria are affected by diabetes mellitus is crucial for understanding the pathogenesis. Examination of mitochondria is complicated by the fact that two mitochondrial subpopulation are present in the cardiomyocyte, interfibrillar mitochondria, which situate between the contractile apparatus and subsarcolemmal mitochondria that exist beneath the plasma membrane. Currently, it is unclear how spatially distinct mitochondrial subpopulations are effected by diabetes mellitus making it difficult to ascertain their specific contribution to diabetic cardiomyopathy. Our long-term goal is to elucidate the mechanisms involved in the pathogenesis of diabetic cardiomyopathy as a prerequisite to the development of therapeutics designed to lessen cardiac complications associated with diabetes mellitus. The purpose of this Administrative Supplement is to incorporate mitochondrial subcompartment assessment into our analyses. This extension is based on the fact that transport of proteins into the mitochondrion is predicated upon specific targeting signals that serve to direct passenger proteins to specific submitochondrial locations (i.e. inner membrane, outer membrane, intermembrane space, matrix). Our rationale for this Administrative Supplement is that by incorporating these analyses, a more comprehensive and accurate picture of the impact of type 1 diabetic insult on mitochondrial subpopulations will be gained.