title: Abnormal levels of human mitochondrial transcription factor A in skeletal muscle in mitochondrial encephalomyopathies.
abstract: Human mitochondrial transcription factor A (hmtTFA or Tfam), a 25-kDa protein encoded by a nuclear gene located on chromosome 10q21, is involved in the control of replication and transcription of mtDNA. To better understand the complex relationship between h-mtTFA and mitochondrial function, we assessed by western blot the levels of h-mtTFA in skeletal muscle from 7 patients affected by mitochondrial diseases (MD) caused by different mtDNA mutations. We related these results to exercise lactate production as well as to the pathologic features of the underlying myopathy. h-mtTFA levels were significantly inversely related to blood lactate and the percent of RRF, borderline to cox negative fibers. Our results indicate that hmtTFA may be involved in the cascade of events which determine functional impairment of MD.
authors.affiliation: Department of Neuroscience, Neurological Clinics, University of Pisa, Via Roma 67, I-56126 Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Siciliano
authors.forename: M
authors.initials: M
authors.lastname: Mancuso
authors.forename: L
authors.initials: L
authors.lastname: Pasquali
authors.forename: M L
authors.initials: ML
authors.lastname: Manca
authors.forename: A
authors.initials: A
authors.lastname: Tessa
authors.forename: A
authors.initials: A
authors.lastname: Iudice
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins; D017354:Point Mutation / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D019344:Lactic Acid