Disease relevance of Tfam

• Glucose increased the Tfam promoter-driven transactivity in L6 (skeletal muscle), HIT (pancreatic beta-cell), and CHO (ovary) cells, but not in HepG2 (hepatoma), HeLa, and CV1 (kidney) cells [1].

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

• None of the inhibitors of protein kinase C, MAP kinase, and PI3 kinase altered the glucose-induced Tfam promoter activity, suggesting that general phosphorylation is involved in its signaling [1].
• In this study, we investigated the mechanism of high glucose-induced Tfam transactivation [1].
• Oxidative stress might not be involved in glucose-induced Tfam expression since treatment with antioxidants such as vitamin C, vitamin E, probucol, or alpha-lipoic acid did not suppress the induction [1].
• The nuclear Tfam protein isoform is absent in the rat and is thus dispensable for mammalian spermatogenesis [4].
• Similar to mice and humans, we found expression of alternate Tfam transcripts, downregulation of mitochondrial Tfam protein levels, and downregulation of mtDNA copy number during rat spermatogenesis [4].

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

• Specific binding of NRF-1 to Tfam promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation [3].
• Immunoblotting data indicated that IMF Tfam protein content was increased by 63% (P < 0.05) at 7 days of stimulation [9].
• RT-PCR experiments have demonstrated that this pseudogene (psi mtTFA) is transcribed in liver tissue [10].

References