Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy

Gabriele Siciliano, Fabio Monzani, Maria Laura Manca, Alessandra Tessa, Nadia Caraccio, Giulia Tozzi, Fiorella Piemonte, Michelangelo Mancuso, Filippo Maria Santorelli, Eleuterio Ferrannini, Luigi Murri

Research output: Contribution to journalArticle

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. Patients and 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.

Original languageEnglish
Pages (from-to)326-333
Number of pages8
JournalMolecular medicine (Cambridge, Mass.)
Volume8
Issue number6
Publication statusPublished - 2002

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Muscular Diseases
Hypothyroidism
Lactic Acid
Muscles
Anaerobic Threshold
Electron Transport Complex IV
Mitochondrial DNA
Thyroid Hormones
Skeletal Muscle
Exercise
Biopsy
Mitochondrial Proteins
Thyroid Diseases
Regulator Genes
Nervous System
Thyroid Gland
mitochondrial transcription factor A
Gene Expression
Control Groups

ASJC Scopus subject areas

  • Genetics

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Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy. / Siciliano, Gabriele; Monzani, Fabio; Manca, Maria Laura; Tessa, Alessandra; Caraccio, Nadia; Tozzi, Giulia; Piemonte, Fiorella; Mancuso, Michelangelo; Santorelli, Filippo Maria; Ferrannini, Eleuterio; Murri, Luigi.

In: Molecular medicine (Cambridge, Mass.), Vol. 8, No. 6, 2002, p. 326-333.

Research output: Contribution to journalArticle

Siciliano, G, Monzani, F, Manca, ML, Tessa, A, Caraccio, N, Tozzi, G, Piemonte, F, Mancuso, M, Santorelli, FM, Ferrannini, E & Murri, L 2002, 'Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy', Molecular medicine (Cambridge, Mass.), vol. 8, no. 6, pp. 326-333.
Siciliano, Gabriele ; Monzani, Fabio ; Manca, Maria Laura ; Tessa, Alessandra ; Caraccio, Nadia ; Tozzi, Giulia ; Piemonte, Fiorella ; Mancuso, Michelangelo ; Santorelli, Filippo Maria ; Ferrannini, Eleuterio ; Murri, Luigi. / Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy. In: Molecular medicine (Cambridge, Mass.). 2002 ; Vol. 8, No. 6. pp. 326-333.
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AU - Siciliano, Gabriele

AU - Monzani, Fabio

AU - Manca, Maria Laura

AU - Tessa, Alessandra

AU - Caraccio, Nadia

AU - Tozzi, Giulia

AU - Piemonte, Fiorella

AU - Mancuso, Michelangelo

AU - Santorelli, Filippo Maria

AU - Ferrannini, Eleuterio

AU - Murri, Luigi

PY - 2002

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