title: Organismal effects of mitochondrial dysfunction.
abstract: Mitochondrial disease can lead to clinical abnormalities in any organ system. Both inherited and spontaneous disorders are known. The spontaneous forms can occur as a mitochondrial DNA (mtDNA) mutation early in embryogenesis or, later in life, as somatic mutations that accumulate with age. The inherited forms may arise from any of >100 characterized mutations in mtDNA or from >200 nuclear gene defects that affect proteins required for mitochondrial function. Most dividing cells survive and interact normally despite their mitochondrial defects. Thus post-mitotic, terminally differentiated cells are preferentially affected in mitochondrial disease. This review emphasizes cellular metabolic co-operation and the structural and biochemical diversity of mitochondria as the framework for understanding the clinical spectrum of mitochondrial disease. The principles of the mitochondrial clinical assessment scale I (MCAS-I) are presented to assist in the development of diagnostic spectra of mitochondrial disease.
authors.affiliation: Mitochondrial and Metabolic Disease Center, University of California, San Diego, School of Medicine, 92103-8467, USA. naviaux@ucsd.edu
authors.forename: R K
authors.initials: RK
authors.lastname: Naviaux
authors.forename: K A
authors.initials: KA
authors.lastname: McGowan
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial