MITOCHONDRIA IN NEUROMUSCULAR DISORDERS

This review considers primary mitochondrial diseases affecting the res piratory chain. As diseases due to mitochondrial DNA defects defy trad itional anatomical classifications, we have not limited our discussion to neuromuscular disorders, but have extended it to include mitochond rial encephalomyopathies. Primary mitochondrial diseases can be due to mutations in either the nuclear or the mitochondrial genome. Nuclear mutations can affect (i) genes encoding enzymatic or structural mitoch ondrial proteins; (ii) translocases; (iii) mitochondrial protein impor tation; and (iv) intergenomic signaling. We review briefly recent mole cular data and outstanding questions regarding these mendelian disorde rs, with special emphasis on cytochrome c oxidase deficiency and coenz yme Q10 deficiency. Mitochondrial DNA mutations fall into three main c ategories: (i) sporadic rearrangements (deletions/duplications); (ii) maternally inherited rearrangements (duplications); and (iii) maternal ly inherited point mutations. We summarize the most common clinical pr esentations and discuss pathogenic mechanisms, which remain largely el usive. Uncertainties about pathogenesis extend to the process of cell death, although excitotoxicity in neurons and apoptosis in muscle seem to have important roles. (C) 1998 Elsevier Science B.V. All rights re served.