Mitochondrial Diseases

A complexity of genetic defects, a unique mode of inheritance, a great variation in clinical expression, and a wide spectrum of pathology characterize mitochondrial diseases. Mitochondria, membrane-bound cellular organelles, are importantly involved in oxidative phos-phorylation (OXPHOS) and, consequently, in supplying the energy essential for the functioning of cells in all organs. Diseases caused by defective oxidative phos-phorylation are generally determined genetically, with both the mitochondrial (mtDNA) and the nuclear (nDNA) genomes involved. Mitochondrial DNA codes 13 proteins of the oxidative phosphorylation system and also a set of transfer RNA (tRNA) and ribosomal RNA. The rest of the proteins (more than 80) are encoded by nDNA. Mutations in either the mtDNA or the nDNA or both can cause diseases. Diseases with mutations in mtDNA are sporadic or transmitted maternally to offsprings of both sexes, but only the daughters transmit the disease to subsequent generations. Maternally inherited diseases are associated with mtDNA deletion, depletion, or missense mutation, and tRNA mutations. Diseases with mutations in nDNA are transmitted in a mendelian mode of inheritance: recessive, dominant, or X-linked. In addition, some diseases are caused by defects in intergenomic communication; that is, mutations in the nDNA gene affect the mtDNA gene, resulting in deletion or depletion of mtDNA. The inheritance of these diseases is also mendelian.

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