Mitochondrial biogenesis defects and neuromuscular disorders

A variety of mitochondrial DNA (mtDNA) defects, ranging from point mutation s and large-scale deletions to severe reduction in the overall quantity of mtDNA (mtDNA depletion), may be associated with neuromuscular disorders. Th e nuclear genome, which encodes most of the proteins involved in mitochondr ial biogenesis (regulation of maintenance, replication, and transcription o f mtDNA), appears to be implicated in many of the mtDNA defects. In this re view, we describe some of the mtDNA defects discovered by our laboratory an d others in patients with neurologic disorders and analyze their potential relationship with the pathways and mechanisms involved in mitochondrial bio genesis. (C) 2000 by Elsevier Science Inc AII rights reserved.