Type 1 diabetes mellitus differentially regulates mitochondrially‐encoded proteins in cardiac mitochondrial subpopulations

Abstract

Mitochondrial dysfunction is a contributing factor in diabetic cardiomyopathy. The mitochondrial genome encodes for thirteen proteins comprising essential constituents of the respiratory chain. Dysregulation of the mitochondrial genome has been shown to correlate with mitochondrial dysfunction. The purpose of this study was to determine whether the protein expression of mitochondrial genome‐encoded proteins were influenced during a type 1 diabetic insult in cardiac subsarcolemmal (SSM) and interfibrillar mitochondria (IFM). Male FVB mice were made diabetic through multiple low‐dose injections of streptozotocin and mitochondrial subpopulations were isolated from cardiac tissue five weeks post‐hyperglycemia. Western blot analyses revealed differential impact on mitochondrial genome encoded proteins from electron transport chain complexes I (ND2, ND3, ND4L, ND5, ND6), III, IV (CO1, CO2, CO3), and V (ATP6) (P<0.05 for all). Of particular interest, was observed significant decreases to mitochondrially‐encoded electron transport chain complex IV proteins CO1 and CO3 within diabetic IFM (P<0.05 for both). The results indicate that type 1 diabetes mellitus differentially regulates mitochondrially‐encoded electron transport chain complex constituents. Further, these effects appear specific for a given mitochondrial subpopulations.