title: Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy.
abstract: BACKGROUND
  Mitochondrial changes have been described in muscle tissue in acquired hypothyroidism. Among the molecular mechanisms by which thyroid hormones regulate expression of nuclear genes encoding for regulatory proteins of mitochondrial respiratory function, the mitochondrial transcription factor A (h-mtTFA) has been proposed to be a target of thyroid hormone action. The aim of this study has been to relate h-mtTFA levels in the skeletal muscle of patients affected by Hashimoto's hypothyroidism and myopathy (HHM) to muscle disease and thyroid status.
  
  
  METHODS
  Eleven HHM patients underwent complete thyroid status and neurologic assessment, along with determination of exercise lactate anaerobic threshold (LT) and muscle biopsy in which h-mtTFA levels were measured and mtDNA was analyzed.
  
  
  RESULTS
  Decreased exercise lactate threshold, presence of cytochrome c oxidase negative fibers, reduction of cytochrome c oxidase activity, and mitochondrial DNA copy number at muscle biopsy were indicative of mitochondrial involvement in these patients. Furthermore, muscle h-mtTFA levels were reduced to a variable extent in comparison with a group of euthyroid controls. The h-mtTFA levels were inversely correlated with TSH and LT lactate, and positively correlated with FT4.
  
  
  CONCLUSIONS
  These results indicate that low levels of the h-mtTFA occur in skeletal muscle of HHM and suggest that abnormal h-mtTFA turnover may be implicated in the pathogenesis of mitochondrial alterations in this disease.
authors.affiliation: Department of Neuroscience, University of Pisa, Italy. gsicilia@neuro.med.unipi.it
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Fabio
authors.initials: F
authors.lastname: Monzani
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Manca
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Nadia
authors.initials: N
authors.lastname: Caraccio
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Eleuterio
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Luigi
authors.initials: L
authors.lastname: Murri
mesh_terms: D001706:Biopsy; D004268:DNA-Binding Proteins; D004576:Electromyography; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000378:metabolism / Q000601:surgery; D009687:Nuclear Proteins / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: 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