Mitochondrial dysfunction in the pathogenesis of hypertrophic cardiomyopathy

Abstract

The pathomorphogenesis of hypertrophic cardiomyopathy is a disruption of the arrangement of muscle cell bundles in the myocardium and is associated with mutations in genes encoding the synthesis of myocardial contractile proteins. Metabolic changes in this pathology are caused by hypertrophy of the interventricular septum due to the disruption of the myocardial contractile apparatus associated with these mutations and mitochondrial dysfunction. Myofiber protein mutations can negatively affect the mitochondria through increased oxidative stress caused by increased ATP demand. The mitochondria are complex organelles with circular DNA and enzyme complexes involved in redox reactions, which cause frequent damage to mitochondrial protein structures and membranes by reactive oxygen species. In this regard, mitochondrial dysfunction can be also caused by mutations in genes encoding mitochondrial proteins, which leads to the disruption of mitophagy and mitochondrial dynamics. The functioning of defective mitochondria is associated with insufficient ATP synthesis and ineffective muscle contraction, which leads to the same consequences at the tissue level as mutations in contractile protein genes. In this review, we tried to summarize the role of mitochondrial dysfunction in the pathomorphogenesis of hypertrophic cardiomyopathy.