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Gene Review

Tfam  -  transcription factor A, mitochondrial

Rattus norvegicus

Synonyms: Transcription factor A, mitochondrial, mtTFA
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Disease relevance of Tfam


High impact information on Tfam

  • 5. Thus, Tfam is the first mammalian protein demonstrated to regulate mtDNA copy number in vivo and is essential for mitochondrial biogenesis and embryonic development [2].
  • Because respiration generates reactive oxygen species as a side-product, we tested the idea that reactive oxygen species regulate Tfam expression through phosphorylation of nuclear respiratory factor (NRF-1) and binding to the Tfam promoter [3].
  • The nuclear expression of mitochondrial transcription factor A (Tfam), which is required for mitochondrial DNA (mtDNA) transcription and replication, must be linked to cellular energy needs [3].
  • In mitochondria-rich rat hepatoma cells that overexpress NRF-1, basal and oxidant-induced increases were found in Tfam expression and mtDNA content [3].
  • NRF-1 gene silencing produced 1:1 knockdown of Tfam expression and decreased mtDNA content [3].

Biological context of Tfam


Anatomical context of Tfam

  • We have now characterized Tfam expression in rat testis to identify conserved features in mammalian spermatogenesis [4].
  • Previous studies have shown significant reduction of Tfam protein levels in mitochondria together with the appearance of abundant testis-specific Tfam mRNA isoforms as spermatogenesis proceeds in both mouse and man [4].
  • PGC-1alpha (peroxisome proliferator-activated receptor [PPARgamma] coactivator-1alpha) activates PPARalpha and mitochondrial transcription factor A (Tfam), which regulate proteins, fatty acid and ATP metabolism (i.e., FAT/CD36, MCAD, and COX I) [5].

Associations of Tfam with chemical compounds

  • The glucose-induced Tfam expression was dose-dependent and cell-type specific [1].
  • Among various monosaccharides, only glucose and fructose increased the Tfam promoter activity [1].
  • Moreover, E2 and flutamide normalized expression of cardiac PGC-1, NRF-2, Tfam, cytochrome-c oxidase subunit IV, and the mitochondrial DNA-encoded gene cytochrome-c oxidase subunit I and beta-ATP synthase, mitochondrial ATP, and cytochrome-c oxidase activity [6].
  • E2 and DPN treatments attenuated the decrease in cardiac mitochondrial ATP, abrogated the T-H-induced lipid accumulation, and normalized PGC-1alpha, PPARalpha, FAT/CD36, MCAD, Tfam, and COX I after T-H [5].

Other interactions of Tfam

  • In this study we tested the hypothesis that ERbeta-mediated cardioprotection is induced via up-regulation of PGC-1alpha through PPARalpha or Tfam-dependent pathway [5].
  • Transcript levels of gene products involved in mtDNA maintenance (Tfam), mitochondrial protein degradation (LON protease), fusion (fuzzy onion homolog), and fission (dynamin-like protein, synaptojanin-2alpha) were also unchanged [7].
  • In contrast with Tfam or the 'housekeeping' beta-actin expressions in which a parallel gradient was observed, no correlation was found between NRF-2 mRNAs and proteins levels, thus suggesting post-transcriptional regulation [8].

Analytical, diagnostic and therapeutic context of Tfam


  1. Regulation of mitochondrial transcription factor A expression by high glucose. Choi, Y.S., Lee, K.U., Pak, Y.K. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  2. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Larsson, N.G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G.S., Clayton, D.A. Nat. Genet. (1998) [Pubmed]
  3. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. Piantadosi, C.A., Suliman, H.B. J. Biol. Chem. (2006) [Pubmed]
  4. Downregulation of Tfam and mtDNA copy number during mammalian spermatogenesis. Rantanen, A., Jansson, M., Oldfors, A., Larsson, N.G. Mamm. Genome (2001) [Pubmed]
  5. Inhibition of cardiac PGC-1alpha expression abolishes ERbeta agonist-mediated cardioprotection following trauma-hemorrhage. Hsieh, Y.C., Choudhry, M.A., Yu, H.P., Shimizu, T., Yang, S., Suzuki, T., Chen, J., Bland, K.I., Chaudry, I.H. FASEB J. (2006) [Pubmed]
  6. PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage. Hsieh, Y.C., Yang, S., Choudhry, M.A., Yu, H.P., Rue, L.W., Bland, K.I., Chaudry, I.H. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  7. Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril. Leary, S.C., Michaud, D., Lyons, C.N., Hale, T.M., Bushfield, T.L., Adams, M.A., Moyes, C.D. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  8. Evidence of tissue-specific, post-transcriptional regulation of NRF-2 expression. Vallejo, C.G., Escrivá, H., Rodríguez-Peña, A. Biochimie (2000) [Pubmed]
  9. Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle. Gordon, J.W., Rungi, A.A., Inagaki, H., Hood, D.A. J. Appl. Physiol. (2001) [Pubmed]
  10. Characterization of the mtTFA gene and identification of a processed pseudogene in rat. Mezzina, M., Reyes, A., D'Errico, I., Gadaleta, G. Gene (2002) [Pubmed]
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