Background. Previously it has been shown that various types of hypertrophic and dilative cardiomyopathy (hCMP, dCMP) can be attributed to disturbed mitochondrial oxidative energy metabolism. Several studies described mutations in mitochondrial DNA-located genes encoding for subunits of respiratory chain complexes, including the cytochrome b gene (MT-CYB), causing CMPs. Methods and Results. In the present study the MT-CYB gene was analysed in 30 patients with hCMP, 40 patients with dCMP, and 50 controls for alterations. Altogether, 27 MT-CYB variants were detected. Twenty-four of them were single nucleotide polymorphisms defining common haplogroups. The variant m.15434C > A was found in a single patient with severe dCMP and assessed as novel mutation, since it was not found in healthy controls or available data sets, and was nonhaplogroup associated with Phylotree. This variant altered an amino acid (L230I) with a high interspecific amino acid conservation index ( C I = 9 7 . 7 %) indicative of the functional importance of the residue. Conclusions. Though the L230I mutation seems to play a causative role for dCMP, prospective studies on yeast or transgenic mice models with defined mutation are warranted to study the pathogenetic impact of this mutation. 1. Introduction Mitochondria play a critical role in both life and death of cardiomyocytes. In healthy cells, their primary function is to meet the high energy demand of the beating heart by providing ATP through oxidative phosphorylation. Mitochondria occupy a large portion of each myocyte and are located between the myofibrils or right below the sarcolemma. The strategic positioning and abundance of mitochondria ensure a highly efficient localized ATP delivery system to support contraction, metabolism, and ion homeostasis [1]. Mitochondrial disorders (MIDs) leading to myocardial disease show a strong age-dependent clinical heterogeneity [2]. Cardiac manifestations of MIDs include arrhythmias and cardiomyopathy (CMP, hypertrophic, (hCMP), dilated (dCMP), restrictive (rCMP), histiocytoid CMP, and noncompaction) [3, 4]. Mitochondria contain their own DNA (mitochondrial DNA (mtDNA)) which is a circular, 16 569 base sequence with 37 genes that encodes for 13 subunits of the respiratory chain complexes, 22 transfer RNAs, and 2 ribosomal RNAs [5]. Mutations in mtDNA-encoded genes influence the production of reactive oxygen species in mice [6] and have been implicated in a large number of human and murine diseases [7]. Some amino acid changes may also improve aerobic capacity and adaptation to new thermal
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