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Acta Myol. 2009 July; 28(1): 36.
PMCID: PMC2859640

I-5. Mitochondrial disorders of the nuclear genome

Production of energy in mitochondria, by the means of oxidative phosphorylation, strictly depends upon respiratory chain complexes which are encoded by both the mitochondrial DNA (mtDNA) and the nuclear genome (nDNA). Respiratory chain complexes are formed, for the most part by subunits, of nuclear origin, while several indispensable complex-assembling proteins are of nuclear origin. Accurate replication and efficient maintenance of mtDNA are also essential for the respiratory chain to function properly. Mitochondrial disorders caused by nDNA defects have been the object of increasing attention in the past few years, establishing themselves as an important and relatively prevalent group of pathologies, and challenging the relevance of diseases caused by inherited mutations of mtDNA itself.

Many metabolic processes, such as oxidation of fatty acids are performed in mitochondria as well as important steps of metal cation metabolism take place in the mitochondrial matrix, such as [Fe-S] cluster synthesis. When these metabolic pathways are disrupted there is production of reactive oxygen species (ROS). Furthermore, mitochondria actively fuse, replicate and move, interacting with the cytoskeleton: all of these functions require the expression of nuclear genes. Proteins involved in mitochondrial motility, fusion and fission include mitofusin 2, whose mutations have been reported in Charcot-Marie-Tooth type 2A2, while hereditary autosomal dominant optic atrophy type 1, in which ROS production is variable, is due to mutation of OPA1, a protein required for fusion of mitochondria and Disorders involving mtDNA replication are referred to, as “intergenomic signalling defects” and may be divided into two main categories: qualitative defects, i.e. multiple mtDNA deletions, and quantitative defects, i.e. mtDNA depletion syndromes. Other relevant nuclear genes related disorders include those for the assembly of respiratory chain subunits (i.e.SURF 1), as well as those coding for enzymes performing critical steps in fatty acid metabolism, their related consequences (CoQ, FAD, FMN).

Articles from Acta Myologica are provided here courtesy of Pacini Editore