TFAM

This gene encodes a key mitochondrial transcription factor containing two high mobility group motifs. The encoded protein also functions in mitochondrial DNA replication and repair. Sequence polymorphisms in this gene are associated with Alzheimer's and Parkinson's diseases. There are pseudogenes for this gene on chromosomes 6, 7, and 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

transcription factor A, mitochondrial

Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (PubMed:29445193, PubMed:32183942).
Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (PubMed:29149603).
In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:20410300).
Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase (PubMed:22037172).
Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites (PubMed:22037172).
Is able to unwind DNA (PubMed:22037172).
Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes (PubMed:1737790).
Required for maintenance of normal levels of mitochondrial DNA (PubMed:22841477, PubMed:19304746).
May play a role in organizing and compacting mitochondrial DNA (PubMed:22037171).

Biological Process mitochondrial respiratory chain complex assemblySource:Ensembl
Biological Process mitochondrial transcriptionSource:UniProtKB1 Publication
Biological Process positive regulation of DNA-templated transcriptionSource:UniProtKB1 Publication
Biological Process transcription initiation at mitochondrial promoterSource:UniProtKB1 Publication

Mitochondrion
Mitochondrion matrix, mitochondrion nucleoid

Mitochondrial DNA depletion syndrome 15, hepatocerebral type (MTDPS15):
An autosomal recessive mitochondrial disorder characterized by severe intrauterine growth restriction, neonatal-onset hypoglycemia and liver dysfunction, mitochondrial DNA depletion in liver and skeletal muscle, and abnormal mitochondrial morphology observed in skeletal muscle. Hepatic pathology includes cirrhosis, steatosis and cholestasis. Progression to liver failure and death is rapid with no evidence of neurological impairment or other organ involvement.

Phosphorylation by PKA within the HMG box 1 impairs DNA binding and promotes degradation by the AAA+ Lon protease.