Genetic basis of mitochondrial myopathies

Mitochondria are double membrane-bound organelles that are present in allnucleated eukaryotic cells and responsible for the production of cellularenergy in the form of ATP. Mitochondrial myopathies and neuropathies orneuromyopathies refer to a heterogeneous group of disorders caused bydysfunction of mitochondria. Mitochondrial disorders can be classifiedaccording to the associated biochemical, genetic defects, or clinical phenotype.Mitochondrial function is under dual genetic control – the 16.6 kbmitochondrial genome encoding just 37 genes with the remaining ~1300proteins of the mitoproteome encoded by nuclear genes. Mitochondrialdysfunction can arise due to defects in either mtDNA or nuclear mitochondrialgenes, and can present in childhood or adulthood in association with vastclinical heterogeneity with symptoms affecting a single organ or tissue, ormultisystem involvement. There is no cure for mitochondrial disease for thevast majority of mitochondrial patients and a genetic diagnosis is thereforecrucial for genetic counselling, recurrence risk calculation and it can modulatethe clinical management of affected patients. mutations in more than 250genes have now been shown to cause mitochondrial disease and thebiochemical, histochemical, immunocytochemical and neuropathologicalcharacterisation of these patients has led to improved diagnostic testingstrategies and novel diagnostic techniques. Developing an effective treatmentfor mitochondrial disease is an enormous challenge that is dependent uponthe integration of clinical understanding of disease progression, moleculargenetic mechanisms, and neuropathological features in mitochondrial disease.