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Description

Transcription factor A, mitochondrial (UniProt: Q00059, also known as mtTFA, Mitochondrial transcription factor 1, MtTF1, Transcription factor 6, TCF-6, Transcription factor 6-like 2, TFAM) is encoded by the TFAM (also known as TCF6, TCF6L2) gene (Gene ID: 7019) in human. TFAM is a DNA binding protein that plays multiple roles in regulating mitochondrial DNA function. As a sequence-specific transcription factor, it binds upstream of the light strand promoter and heavy strand promoter 1 to activate initiation of transcription. It is a component of the mitochondrial transcription initiation complex (composed of TFB2M, TFAM and POLRMT). In this complex, TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. TFAM is required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase. TFAM contains two HMG boxes (aa 50-118 and 155-219). Phosphorylation by protein kinase A within the HMG box 1 is shown to impair its DNA binding and promotes its degradation by AAA+ Lon protease. Mutations in TFAM gene are known to cause hepatocerebral type of mitochondrial DNA depletion syndrome that is characterized by severe intrauterine growth restriction, neonatal-onset hypoglycemia and liver dysfunction. In this disease hepatic pathology includes cirrhosis, steatosis and cholestasis that leads to liver failure. (Ref.: Wang, YE., et al. (2013). PLoS ONE. 8(8), e74513).