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Import of mitochondrial transcription factor A (TFAM) into rat liver mitochondria stimulates transcription of mitochondrial DNA.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2003 Sep 01; Vol. 31 (17), pp. 5039-47. - Publication Year :
- 2003
-
Abstract
- Mitochondrial transcription factor A (TFAM) has been shown to stimulate transcription from mitochondrial DNA promoters in vitro. In order to determine whether changes in TFAM levels also regulate RNA synthesis in situ, recombinant human precursor proteins were imported into the matrix of rat liver mitochondria. After uptake of wt-TFAM, incorporation of [alpha-32P]UTP into mitochondrial mRNAs as well as rRNAs was increased 2-fold (P < 0.05), whereas import of truncated TFAM lacking 25 amino acids at the C-terminus had no effect. Import of wt-TFAM into liver mitochondria from hypothyroid rats stimulated RNA synthesis up to 4-fold. We conclude that the rate of transcription is submaximal in freshly isolated rat liver mitochondria and that increasing intra-mitochondrial TFAM levels is sufficient for stimulation. The low transcription rate associated with the hypothyroid state observed in vivo as well as in organello seems to be a result of low TFAM levels, which can be recovered by treating animals with T3 in vivo or by importing TFAM in organello. Thus, this protein meets the criteria for being a key factor in regulating mitochondrial gene expression in vivo.
- Subjects :
- Animals
Female
Humans
Hyperthyroidism genetics
Hyperthyroidism metabolism
Hypothyroidism genetics
Hypothyroidism metabolism
Mitochondria, Liver genetics
Protein Transport
RNA genetics
RNA metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Mitochondrial
Rats
Rats, Sprague-Dawley
Transcription Factors genetics
Transcription, Genetic
DNA, Mitochondrial genetics
DNA-Binding Proteins
Mitochondria, Liver metabolism
Mitochondrial Proteins
Nuclear Proteins
Trans-Activators
Transcription Factors metabolism
Xenopus Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 31
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 12930954
- Full Text :
- https://doi.org/10.1093/nar/gkg717