Gene Symbol: Tfam
Description: transcription factor A, mitochondrial
Alias: Mttfa, transcription factor A, mitochondrial
Species: rat
Products:     Tfam

Top Publications

  1. Gangelhoff T, Mungalachetty P, Nix J, Churchill M. Structural analysis and DNA binding of the HMG domains of the human mitochondrial transcription factor A. Nucleic Acids Res. 2009;37:3153-64 pubmed publisher
    The mitochondrial transcription factor A (mtTFA) is central to assembly and initiation of the mitochondrial transcription complex...
  2. Larsson N, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet. 1998;18:231-6 pubmed
    ..We have disrupted the mouse gene for mitochondrial transcription factor A (Tfam; formerly known as m-mtTFA) by gene targetting of loxP-sites followed by cre-mediated excision in vivo...
  3. Gaspari M, Falkenberg M, Larsson N, Gustafsson C. The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells. EMBO J. 2004;23:4606-14 pubmed
    ..depends on three proteins: mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM) and mitochondrial transcription factor B2 (TFB2M)...
  4. Dinardo M, Musicco C, Fracasso F, Milella F, Gadaleta M, Gadaleta G, et al. Acetylation and level of mitochondrial transcription factor A in several organs of young and old rats. Biochem Biophys Res Commun. 2003;301:187-91 pubmed
    To gain further information on the role of mitochondrial transcription factor A (TFAM) in mitochondrial biogenesis, we studied the post-translational modifications of the protein in 6- and 28-month-old rat liver...
  5. Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D, et al. P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA. Cancer Res. 2003;63:3729-34 pubmed
    Mitochondrial transcription factor A (mtTFA; also designated Tfam) is necessary for both transcription and maintenance of mitochondrial DNA. mtTFA preferentially recognizes cisplatin-damaged DNA, as well as oxidized DNA...
  6. Zhong Y, Hu Y, Chen B, Peng W, Sun Y, Yang Y, et al. Mitochondrial transcription factor A overexpression and base excision repair deficiency in the inner ear of rats with D-galactose-induced aging. FEBS J. 2011;278:2500-10 pubmed publisher
    ..This study also provides new insights into the development of presbycusis. ..
  7. Alcolea M, Colom B, Lladó I, Gianotti M, Garcia Palmer F. Mitochondrial transcription factor A (TFAM) is increased in rat embryo during placentation and associated with mitochondrial differentiation. Cell Physiol Biochem. 2006;17:79-88 pubmed
    ..single strand DNA binding protein (mtSSB)), mtDNA transcription (mitochondrial transcription factor A (TFAM)), as well as in mitochondrial function (cytochrome c oxidase subunit I (COXI))...
  8. Wu K, Wu C, Chao Y, Hung C, Chan J. Impaired Nrf2 regulation of mitochondrial biogenesis in rostral ventrolateral medulla on hypertension induced by systemic inflammation. Free Radic Biol Med. 2016;97:58-74 pubmed publisher
    ..DNA-encoded transcription factors for mitochondrial biogenesis, including mitochondrial transcription factor A (TFAM) and nuclear factor erythroid-derived 2-like 2 (Nrf2), and suppression of nuclear translocation of the ..
  9. Picca A, Pesce V, Fracasso F, Joseph A, Leeuwenburgh C, Lezza A. Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver. PLoS ONE. 2013;8:e74644 pubmed publisher
    ..we found an age-related decrease in mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (TFAM) amount, fully prevented by CR...

More Information


  1. Santos J, Kowluru R. Impaired transport of mitochondrial transcription factor A (TFAM) and the metabolic memory phenomenon associated with the progression of diabetic retinopathy. Diabetes Metab Res Rev. 2013;29:204-13 pubmed publisher
    ..In the transcription and replication of mtDNA, nuclear-encoded mitochondrial transcription factor A (TFAM) is considered a key activator...
  2. Chaturvedi R, Calingasan N, Yang L, Hennessey T, Johri A, Beal M. Impairment of PGC-1alpha expression, neuropathology and hepatic steatosis in a transgenic mouse model of Huntington's disease following chronic energy deprivation. Hum Mol Genet. 2010;19:3190-205 pubmed publisher
    ..In the striatum of the HD mice, the baseline levels of PGC-1alpha, NRF1, NRF2, Tfam, COX-II, PPARdelta, CREB and ERRalpha mRNA and mitochondrial DNA (mtDNA), were significantly reduced...
  3. Li H, Wang J, Wilhelmsson H, Hansson A, Thoren P, Duffy J, et al. Genetic modification of survival in tissue-specific knockout mice with mitochondrial cardiomyopathy. Proc Natl Acad Sci U S A. 2000;97:3467-72 pubmed
    ..The gene for mouse mitochondrial transcription factor A, Tfam (also called mtTFA), a nucleus-encoded key regulator of mtDNA expression, was targeted with loxP sites (Tfam(loxP)) and disrupted in ..
  4. Nishio Y, Kanazawa A, Nagai Y, Inagaki H, Kashiwagi A. Regulation and role of the mitochondrial transcription factor in the diabetic rat heart. Ann N Y Acad Sci. 2004;1011:78-85 pubmed
    ..of mitochondrial DNA could not be explained by mRNA or protein contents of mitochondrial transcription factor (mtTFA), but mtTFA binding to the promoter sequence of mitochondrial DNA, assessed by gel-shift assay, was attenuated in ..
  5. Piantadosi C, Suliman H. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J Biol Chem. 2006;281:324-33 pubmed
    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...
  6. Watanabe A, Arai M, Koitabashi N, Niwano K, Ohyama Y, Yamada Y, et al. Mitochondrial transcription factors TFAM and TFB2M regulate Serca2 gene transcription. Cardiovasc Res. 2011;90:57-67 pubmed publisher
    ..Messenger RNA (mRNA) for these enzymes is transcribed by mitochondrial transcription factors A (TFAM) and B2 (TFB2M)...
  7. Litonin D, Sologub M, Shi Y, Savkina M, Anikin M, Falkenberg M, et al. Human mitochondrial transcription revisited: only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro. J Biol Chem. 2010;285:18129-33 pubmed publisher
    ..We found that TFAM and TFB2M act synergistically and increase transcription efficiency 100-200-fold as compared with RNA polymerase ..
  8. Santos J, Kowluru R. Role of mitochondria biogenesis in the metabolic memory associated with the continued progression of diabetic retinopathy and its regulation by lipoic acid. Invest Ophthalmol Vis Sci. 2011;52:8791-8 pubmed publisher
    ..receptor-? coactivator-1? [PGC1], nuclear respiratory factor 1 [NRF1], mitochondrial transcriptional factor [TFAM]) were analyzed in the retina from streptozotocin-diabetic rats maintained in poor or good control for 12 months (..
  9. Chaung W, Wu R, Ji Y, Dong W, Wang P. Mitochondrial transcription factor A is a proinflammatory mediator in hemorrhagic shock. Int J Mol Med. 2012;30:199-203 pubmed publisher
    ..Mitochondrial transcription factor A (TFAM) is a transcription factor for mitochondrial DNA...
  10. Yin W, Signore A, Iwai M, Cao G, Gao Y, Chen J. Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain injury. Stroke. 2008;39:3057-63 pubmed publisher
    ..receptor coactivator-1 (PGC-1), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM), were examined by Western blot and RT-PCR...
  11. Fredriksson K, Tjader I, Keller P, Petrovic N, Ahlman B, Scheele C, et al. Dysregulation of mitochondrial dynamics and the muscle transcriptome in ICU patients suffering from sepsis induced multiple organ failure. PLoS ONE. 2008;3:e3686 pubmed publisher
    ..there was partial activation of the mitochondrial biogenesis pathway involving NRF2alpha/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function...
  12. Gaweda Walerych K, Safranow K, Jasinska Myga B, Bialecka M, Klodowska Duda G, Rudzinska M, et al. PARK2 variability in Polish Parkinson's disease patients--interaction with mitochondrial haplogroups. Parkinsonism Relat Disord. 2012;18:520-4 pubmed publisher
    ..Parkin complexed with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes mitochondrial biogenesis, which is abolished by PARK2 gene mutations...
  13. Pietrowska M, Kołodziejczyk I, Widłak P. Mitochondrial transcription factor A is the major protein in rodent hepatocytes that recognizes DNA lesions induced by N-acetoxy-acetylaminofluorene. Acta Biochim Pol. 2006;53:777-82 pubmed
    ..from rat tissue and analyzed it by mass spectrometry and identified it as mitochondrial transcription factor A (TFAM). Experiments with bacterially expressed recombinant TFAM confirmed its high affinity for DNA damaged by AAAF...
  14. Picca A, Pesce V, Fracasso F, Joseph A, Leeuwenburgh C, Lezza A. A comparison among the tissue-specific effects of aging and calorie restriction on TFAM amount and TFAM-binding activity to mtDNA in rat. Biochim Biophys Acta. 2014;1840:2184-91 pubmed publisher
    Mitochondrial Transcription Factor A (TFAM) is regarded as a histone-like protein of mitochondrial DNA (mtDNA), performing multiple functions for this genome...
  15. Larsson N, Garman J, Oldfors A, Barsh G, Clayton D. A single mouse gene encodes the mitochondrial transcription factor A and a testis-specific nuclear HMG-box protein. Nat Genet. 1996;13:296-302 pubmed
    Mitochondrial transcription factor A (mtTFA) is a key regulator of mammalian mitochondrial DNA transcription...
  16. Tryon L, Crilly M, Hood D. Effect of denervation on the regulation of mitochondrial transcription factor A expression in skeletal muscle. Am J Physiol Cell Physiol. 2015;309:C228-38 pubmed publisher
    The purpose of this study was to determine how the expression of mitochondrial transcription factor A (Tfam), a protein that governs mitochondrial DNA (mtDNA) transcription and replication, is regulated during a state of reduced organelle ..
  17. Morimoto N, Miyazaki K, Kurata T, Ikeda Y, Matsuura T, Kang D, et al. Effect of mitochondrial transcription factor a overexpression on motor neurons in amyotrophic lateral sclerosis model mice. J Neurosci Res. 2012;90:1200-8 pubmed publisher
    ..susceptible to oxidative damage and has little potential for repair, although mitochondrial transcription factor A (TFAM) plays essential roles in maintaining mitochondrial DNA by reducing oxidative stress, promoting mtDNA transcription,..
  18. Shankar K, Zhong Y, Kang P, Lau F, Blackburn M, Chen J, et al. Maternal obesity promotes a proinflammatory signature in rat uterus and blastocyst. Endocrinology. 2011;152:4158-70 pubmed publisher
    ..proinflammatory genes (CCL4 and CCL5) increased and expression of antioxidant (GPx3) and mitochondrial (TFAM and NRF1) genes decreased in the obese embryos...
  19. Han Y, Lin Y, Xie N, Xue Y, Tao H, Rui C, et al. Impaired mitochondrial biogenesis in hippocampi of rats with chronic seizures. Neuroscience. 2011;194:234-40 pubmed publisher
    ..receptor gamma coactivator-1?, nuclear respiratory factor-1, and mitochondrial transcription factor A (Tfam), but depended on reduced Tfam-DNA binding activity...
  20. Bogenhagen D, Martin D, Koller A. Initial steps in RNA processing and ribosome assembly occur at mitochondrial DNA nucleoids. Cell Metab. 2014;19:618-29 pubmed publisher
    ..These results provide insight into the landscape of binding events required for mitochondrial ribosome assembly and firmly establish the mtDNA nucleoid as a control center for mitochondrial biogenesis. ..
  21. Kanazawa A, Nishio Y, Kashiwagi A, Inagaki H, Kikkawa R, Horiike K. Reduced activity of mtTFA decreases the transcription in mitochondria isolated from diabetic rat heart. Am J Physiol Endocrinol Metab. 2002;282:E778-85 pubmed
    To evaluate abnormalities in the mitochondrial transcription factor A (mtTFA) function as a cause of mitochondrial dysfunction in diabetes, we measured the mRNA contents of the proteins consisting of the mitochondrial respiratory chain ..
  22. Rantanen A, Jansson M, Oldfors A, Larsson N. Downregulation of Tfam and mtDNA copy number during mammalian spermatogenesis. Mamm Genome. 2001;12:787-92 pubmed
    Mitochondrial transcription factor A (Tfam) is required for mtDNA maintenance, and mitochondrial Tfam protein levels directly affect mtDNA copy number...
  23. Ngo H, Kaiser J, Chan D. The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. Nat Struct Mol Biol. 2011;18:1290-6 pubmed publisher
    b>Tfam (transcription factor A, mitochondrial), a DNA-binding protein with tandem high-mobility group (HMG)-box domains, has a central role in the expression, maintenance and organization of the mitochondrial genome...
  24. Patki G, Lau Y. Impact of exercise on mitochondrial transcription factor expression and damage in the striatum of a chronic mouse model of Parkinson's disease. Neurosci Lett. 2011;505:268-72 pubmed publisher
  25. Zhang Q, Wu Y, Zhang P, Sha H, Jia J, Hu Y, et al. Exercise induces mitochondrial biogenesis after brain ischemia in rats. Neuroscience. 2012;205:10-7 pubmed publisher
    ..7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also ..
  26. Suarez J, Hu Y, Makino A, Fricovsky E, Wang H, Dillmann W. Alterations in mitochondrial function and cytosolic calcium induced by hyperglycemia are restored by mitochondrial transcription factor A in cardiomyocytes. Am J Physiol Cell Physiol. 2008;295:C1561-8 pubmed publisher
    Mitochondrial transcription factor A (TFAM) is essential for mitochondrial DNA transcription and replication. TFAM transcriptional activity is decreased in diabetic cardiomyopathy; however, the functional implications are unknown...
  27. Alvarez V, Corao A, Sánchez Ferrero E, De Mena L, Alonso Montes C, Huerta C, et al. Mitochondrial transcription factor A (TFAM) gene variation in Parkinson's disease. Neurosci Lett. 2008;432:79-82 pubmed publisher
    ..The mitochondrial transcription factor A (TFAM) controls the transcription of mtDNA and regulates the mtDNA-copy number, thus being important for maintaining ATP ..
  28. Belin A, Björk B, Westerlund M, Galter D, Sydow O, Lind C, et al. Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease. Neurosci Lett. 2007;420:257-62 pubmed
    ..Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional ..
  29. Inagaki H, Hayashi T, Matsushima Y, Lin K, Maeda S, Ichihara S, et al. Isolation of rat mitochondrial transcription factor A (r-Tfam) cDNA. DNA Seq. 2000;11:131-5 pubmed
    We have isolated rat mitochondrial transcription factor A (Tfam; formerly known as mtTFA) cDNA clones from a rat cerebellum cDNA library using human Tfam cDNA as a probe...
  30. Maruszak A, Safranow K, Branicki W, Gaweda Walerych K, Pośpiech E, Gabryelewicz T, et al. The impact of mitochondrial and nuclear DNA variants on late-onset Alzheimer's disease risk. J Alzheimers Dis. 2011;27:197-210 pubmed publisher
    ..haplogroups, and polymorphisms in nuclear genes essential for mitochondrial biogenesis and function (PGC-1? TFAM) to late-onset Alzheimer's disease (LOAD) risk...
  31. Yoshida T, Azuma H, Aihara K, Fujimura M, Akaike M, Mitsui T, et al. Vascular smooth muscle cell proliferation is dependent upon upregulation of mitochondrial transcription factor A (mtTFA) expression in injured rat carotid artery. Atherosclerosis. 2005;178:39-47 pubmed
    ..We hypothesized that mitochondrial transcription factor A (mtTFA), a prerequisite factor for the transcription and replication of mtDNA, may be upregulated in VSMC of injured rat ..
  32. Mezzina M, Reyes A, D Errico I, Gadaleta G. Characterization of the mtTFA gene and identification of a processed pseudogene in rat. Gene. 2002;286:105-12 pubmed
    ..Among these there is the mitochondrial transcription factor A (mtTFA or Tfam)...
  33. Smith B, Mukai K, Lally J, Maher A, Gurd B, Heigenhauser G, et al. AMP-activated protein kinase is required for exercise-induced peroxisome proliferator-activated receptor co-activator 1 translocation to subsarcolemmal mitochondria in skeletal muscle. J Physiol. 2013;591:1551-61 pubmed publisher
    ..peroxisome proliferator-activated receptor ? co-activator 1? (PGC-1?) and mitochondrial transcription factor A (Tfam) have been implicated in the direct regulation of the mitochondrial genome in mice, although SS and IMF differences ..
  34. Gauthier B, Wiederkehr A, Baquie M, Dai C, Powers A, Kerr Conte J, et al. PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. Cell Metab. 2009;10:110-8 pubmed publisher
    ..Transcript profiling revealed suppression of nuclear-encoded mitochondrial factor A (TFAM). Herein, we show that Pdx1 suppression in adult mice reduces islet TFAM expression coinciding with hyperglycemia...
  35. Wang J, Silva J, Gustafsson C, Rustin P, Larsson N. Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression. Proc Natl Acad Sci U S A. 2001;98:4038-43 pubmed
    ..Apoptosis was studied in embryos with homozygous disruption of the mitochondrial transcription factor A gene (Tfam) and tissue-specific Tfam knockout animals with severe respiratory chain deficiency in the heart...
  36. Pastukh V, Gorodnya O, Gillespie M, Ruchko M. Regulation of mitochondrial genome replication by hypoxia: The role of DNA oxidation in D-loop region. Free Radic Biol Med. 2016;96:78-88 pubmed publisher
    ..Ogg1 overexpression also reduced binding of mitochondrial transcription factor A (TFAM) to both regulatory and coding regions of the mitochondrial genome without altering total abundance of TFAM in ..
  37. Taherzadeh Fard E, Saft C, Akkad D, Wieczorek S, Haghikia A, Chan A, et al. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease. Mol Neurodegener. 2011;6:32 pubmed publisher the nuclear respiratory factor 1 gene, NRF-1, and the mitochondrial transcription factor A, encoded by TFAM showed nominally significant association with AO of HD...
  38. Remels A, Schrauwen P, Broekhuizen R, Willems J, Kersten S, Gosker H, et al. Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD. Eur Respir J. 2007;30:245-52 pubmed
    ..PGC)-1alpha in regulation of skeletal muscle morphology and metabolism, and mitochondrial transcription factor A (TFAM) has been implicated in the process of mitochondrial biogenesis...
  39. Choi Y, Lee H, Pak Y. Characterization of the 5'-flanking region of the rat gene for mitochondrial transcription factor A (Tfam). Biochim Biophys Acta. 2002;1574:200-4 pubmed
    Mitochondrial transcription factor A (Tfam) is essential for the initiation of transcription and the replication of mitochondrial DNA (mtDNA)...