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Published on: January 19, 2017

Induction of mitochondrial biogenesis is a maladaptive mechanism in mitochondrial cardiomyopathies

Mariangela Sebastiani1, Carla Giordano, Chiara Nediani

  • 1Dipartimento di Medicina Sperimentale, Polo Pontino, Sapienza, Università di Roma, Rome, Italy.

Journal of the American College of Cardiology
|October 2, 2007
PubMed
Abstract

Insights

Mitochondrial deoxyribonucleic acid (mtDNA) defects in mitochondrial cardiomyopathies (MIC) cause excessive mitochondrial proliferation, leading to cardiac remodeling. This mitochondrial biogenesis is a maladaptive response, not just energy deficiency.

Area of Science:

  • Cardiovascular Research
  • Mitochondrial Biology
  • Molecular Cardiology

Background:

  • Mitochondrial cardiomyopathies (MIC) result from mitochondrial genome defects, leading to cardiac dysfunction.
  • The molecular links between mitochondrial deoxyribonucleic acid (mtDNA) defects and cardiac remodeling remain unclear.
  • Increased mitochondrial reactive oxygen species (ROS) and proliferation may contribute to cardiac dysfunction in MIC.

Purpose of the Study:

  • To elucidate the molecular mechanisms connecting human mtDNA dysfunction to cardiac remodeling.
  • To investigate the role of mitochondrial biogenesis and ROS in MIC.

Main Methods:

  • Morphologic and molecular analyses were performed on failing hearts from MIC patients, ischemic heart disease (IHD), dilated cardiomyopathies (DCM), and nonfailing controls.
  • Gene expression related to mitochondrial function, metabolism, and oxidative stress was assessed.

Main Results:

  • MIC hearts exhibited significant mitochondrial proliferation, myofibril displacement, and increased mtDNA content.
  • Genes for mitochondrial biogenesis, fatty acid, and glucose metabolism were upregulated in MIC but downregulated in DCM and IHD.
  • MIC hearts showed increased mitochondrial ROS production, paralleled by upregulation of uncoupling proteins and antioxidant genes, though enzyme activity was not significantly increased.

Conclusions:

  • Mitochondrial biogenesis in MIC is a maladaptive response, contributing to cardiac remodeling beyond simple energy deficiency.
  • These findings may extend to other metabolic cardiomyopathies.

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