Struture
The mitochondrial transcription factor A is a 25 kDa protein belonging to the high protein group mobility, which are characterized by binding to DNA through registered HMG-box domains and important in the organization and chromatin function. TFAM features two HMG-box domains in the form of "L" composed of three α-helices, separated by a linker of 27 amino acid residues and a loaded C-terminal tail, of 25 waste. The TFM HMG-box domains that present tandem repetitions and are stabilized by hydrophobic nuclei. [1]
Function
Human mitochondrial transcription factor A (TFAM) is essentialfor mitochondrial DNA (mtDNA) synthesis and expression aswell as mtDNA packagin. TFAM is the most abundant componentof mitochondrial nucleoids, which are protein complexesassociated with mtDNA that orchestrate genome replication,expression, and inheritance TFAM is involved in many cellular functions including mtDNA transcription, maintenance, repair, and replication and its activity is vital in
the maintenance of mtDNA copy number.The in vivo packaging of mtDNA by TFAMhas been estimated at 35–50 to 1,000–1,700 molecules per genome. Higher TFAM:mtDNA ratios are interpreted as resulting in tightercompaction of mtDNA and reduced accessibility to transcrip-tion, replication, or repair factors, whereas lower ratios are pre-dicted to permit increased accessibility.[2]
[3]
[4]
CICLE
► cAMP-dependent protein kinase (PKA) serine phosphorylates TFAM within HMG1 ► HMG1 phosphorylation of TFAM impairs DNA binding and transcription activation ► Lon protease selectively degrades DNA-free TFAM and is inhibited by bortezomib ► Lon knockdown stabilizes TFAM in mtDNA-deficient cells and upregulates mtDNA. [5]
Disease
A positive relationship is reported between mDNA copy number, glucose consumption and ATP production in melanoma cells. [6] In addition, a new hepatocerebral mtDNA depletion syndrome caused by TFAM deficiency is presented in the literature. The disease is characterized due to liver failure from neonatal onset progressing to death. Liver pathology revealed cirrhosis, steatosis, cholestasis and mitochondrial changes. It was observed that mtDNA is depleted in the liver and skeletal muscles and provides evidence that this results in decreased expression of the TFAM protein, reduced drial function and nucleoid formation.[7]
Aging and Calorie Restriction
Structural highlights
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