Protective Mechanisms of Mitochondria and Heart Function in Diabetes

Miguel A. Aon, Carlo G. Tocchetti, Niraj Bhatt, Nazareno Paolocci, Sonia Cortassa

Research output: Contribution to journalArticle

Abstract

Significance: 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). Critical Issues: 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. Recent Advances: 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. Future Directions: 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.

Original languageEnglish (US)
Pages (from-to)1563-1586
Number of pages24
JournalAntioxidants and Redox Signaling
Volume22
Issue number17
DOIs
StatePublished - Jun 10 2015

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Heart Mitochondria
Mitochondria
Medical problems
Diabetic Cardiomyopathies
Oxidation-Reduction
Lipids
Glucose
Fatty Acids
Thioredoxins
Aptitude
Workload
Mitochondrial DNA
Biological Availability
Nutrients
Glutathione
Reactive Oxygen Species
Up-Regulation
Antioxidants
Adenosine Triphosphate
Learning

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Protective Mechanisms of Mitochondria and Heart Function in Diabetes. / Aon, Miguel A.; Tocchetti, Carlo G.; Bhatt, Niraj; Paolocci, Nazareno; Cortassa, Sonia.

In: Antioxidants and Redox Signaling, Vol. 22, No. 17, 10.06.2015, p. 1563-1586.

Research output: Contribution to journalArticle

Aon, Miguel A. ; Tocchetti, Carlo G. ; Bhatt, Niraj ; Paolocci, Nazareno ; Cortassa, Sonia. / Protective Mechanisms of Mitochondria and Heart Function in Diabetes. In: Antioxidants and Redox Signaling. 2015 ; Vol. 22, No. 17. pp. 1563-1586.
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