title: Protective mechanisms of mitochondria and heart function in diabetes.
abstract: CONCLUSIONS
  The heart depends on continuous mitochondrial ATP supply and maintained redox balance to properly develop force, particularly under increased workload. During diabetes, however, myocardial energetic-redox balance is perturbed, contributing to the systolic and diastolic dysfunction known as diabetic cardiomyopathy (DC).
  
  
  RESULTS
  How these energetic and redox alterations intertwine to influence the DC progression is still poorly understood. Excessive bioavailability of both glucose and fatty acids (FAs) play a central role, leading, among other effects, to mitochondrial dysfunction. However, where and how this nutrient excess affects mitochondrial and cytoplasmic energetic/redox crossroads remains to be defined in greater detail.
  
  
  BACKGROUND
  We review how high glucose alters cellular redox balance and affects mitochondrial DNA. Next, we address how lipid excess, either stored in lipid droplets or utilized by mitochondria, affects performance in diabetic hearts by influencing cardiac energetic and redox assets. Finally, we examine how the reciprocal energetic/redox influence between mitochondrial and cytoplasmic compartments shapes myocardial mechanical activity during the course of DC, focusing especially on the glutathione and thioredoxin systems.
  
  
  CONCLUSIONS
  Protecting mitochondria from losing their ability to generate energy, and to control their own reactive oxygen species emission is essential to prevent the onset and/or to slow down DC progression. We highlight mechanisms enforced by the diabetic heart to counteract glucose/FAs surplus-induced damage, such as lipid storage, enhanced mitochondria-lipid droplet interaction, and upregulation of key antioxidant enzymes. Learning more on the nature and location of mechanisms sheltering mitochondrial functions would certainly help in further optimizing therapies for human DC.
authors: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Miguel A
authors: MA
authors: Aon
authors: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Carlo G
authors: CG
authors: Tocchetti
authors: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Niraj
authors: N
authors: Bhatt
authors: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Nazareno
authors: N
authors: Paolocci
authors: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Sonia
authors: S
authors: Cortassa
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D004272:DNA, Mitochondrial; D005227:Fatty Acids; D005947:Glucose