Abstract
Mitochondrial diseases are defined by a respiratory chain dysfunction and in most of the cases manifest as multisystem disorders with predominant expression in muscles and nerves and may be caused by mutations in mitochondrial (mtDNA) or nuclear (nDNA) genomes. Most of the proteins involved in respiratory chain function are nuclear encoded, although 13 subunits of respiratory chain complexes (together with 2 rRNAs and 22 tRNAs necessary for their translation) encoded by mtDNA are essential for cell function. nDNA encodes not only respiratory chain subunits but also all the proteins responsible for mtDNA maintenance, especially those involved in replication, as well as other proteins necessary for the transcription and copy number control of this multicopy genome. Mutations in these genes can cause secondary instability of the mitochondrial genome in the form of depletion (decreased number of mtDNA molecules in the cell), vast multiple deletions or accumulation of point mutations which in turn leads to mitochondrial diseases inherited in a Mendelian fashion. The list of genes involved in mitochondrial DNA maintenance is long, and still incomplete.
Highlights
Mitochondrial diseases are defined by a respiratory chain dysfunction and in most of the cases manifest as multisystem disorders with predominant expression in muscles and nerves and may be caused by mutations in mitochondrial or nuclear genomes
Most of the proteins involved in respiratory chain function are nuclear encoded, 13 subunits of respiratory chain complexes encoded by mitochondrial DNA (mtDNA) are essential for cell function. nDNA encodes respiratory chain subunits and all the proteins responsible for mtDNA maintenance, especially those involved in replication, as well as other proteins necessary for the transcription and copy number control of this multicopy genome
Mutations in these genes can cause secondary instability of the mitochondrial genome in the form of depletion, vast multiple deletions or accumulation of point mutations which in turn leads to mitochondrial diseases inherited in a Mendelian fashion
Summary
Mitochondria are cytoplasmic organelles with a double phospholipid membrane and are present in almost all eukaryotic cells. Mitochondria are necessary for cell form and function. Their best recognized role is to generate energy by oxidative phosphorylation, but they play a key role in synthesis of iron–sulfur centers, fatty acid oxidation, chemical signaling (Ca2+ signaling) and programmed cell death. All other proteins (over 2000) required for the proper function of all mitochondrial biochemical pathways, including the rest of the subunits of respiratory complexes, are encoded by nuclear genes. This means that mitochondrial DNA expression, maintenance, copy number regulation, and repair. The heteroplasmy level of pathogenic variants correlates with the phenotype to some extent
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