User:Milena Ortiz Ribeiro/Sandbox 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.^[1]

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Disease

A positive relationship is reported between mDNA copy number, glucose consumption and ATP production in melanoma cells. ^[5] 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.^[6]

Aging and Calorie Restriction

Structural highlights

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